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[ CAS No. 700-36-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

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2D 3D

Chemical Structure| 700-36-7

Chemical Structure| 700-36-7

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Quality Control of [ 700-36-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 700-36-7 ]

Product Details of [ 700-36-7 ]

CAS No. :	700-36-7	MDL No. :	MFCD00792441
Formula :	C₆H₃BrFNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VGYVBEJDXIPSDL-UHFFFAOYSA-N
M.W :	220.00	Pubchem ID :	2756993
Synonyms :

Calculated chemistry of [ 700-36-7 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	42.92
TPSA :	45.82 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.94 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.64
Log Po/w (XLOGP3) :	2.4
Log Po/w (WLOGP) :	2.92
Log Po/w (MLOGP) :	2.06
Log Po/w (SILICOS-IT) :	0.81
Consensus Log Po/w :	1.96

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.05
Solubility :	0.194 mg/ml ; 0.000884 mol/l
Class :	Soluble
Log S (Ali) :	-3.0
Solubility :	0.218 mg/ml ; 0.000991 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.92
Solubility :	0.266 mg/ml ; 0.00121 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.86

Safety of [ 700-36-7 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 700-36-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 700-36-7 ]
Downstream synthetic route of [ 700-36-7 ]

[ 700-36-7 ] Synthesis Path-Upstream 1~12

1
[ 700-36-7 ]
[ 399-72-4 ]

Reference： [1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 44, p. 10511 - 10515
[2] Patent: CN106631968, 2017, A,

2
[ 371-40-4 ]
[ 700-36-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-Bromosuccinimide In dichloromethane at 0 - 20℃;	To a solution of 4-fluoroaniline (20 g, 180 mmol) in dichloromethane (100 mL) at 0° C. was added N-bromosuccinimide (34 g, 180 mmol, in 60 mL dichloromethane) dropwise. The mixture was stirred at room temperature overnight. The reaction was washed with saturated sodium sulfite, saturated sodium bicarbonate, and brine and concentrated to provide the title compound (34 g, 154.5 mmol, 100percent). ¹H NMR (400 MHz, CDCl₃) δ ppm 7.12-7.21 (m, 1H), 7.47 (dd, J=7.60, J=2.40, 1H), (dd, J=9.60, J=6.40, 1H).

Reference： [1] Patent: US2008/300242, 2008, A1, . Location in patent: Page/Page column 62

3
[ 320-98-9 ]
[ 700-36-7 ]

Yield	Reaction Conditions	Operation in experiment
33%	With 2.9-dimethyl-1,10-phenanthroline; oxygen; copper (I) acetate; silver sulfate; sodium bromide In dimethyl sulfoxide at 160℃; for 24 h; Schlenk technique	Silak reaction tube equipped with a magnetic stirrer was charged with 6.2 mg of silver sulfate,36.3 mg of copper acetate, 12.5 mg of 2,9-dimethyl-1,10-o-phenanthroline,37 mg of 2-nitro-5-fluorobenzoic acid and 30.9 mg of sodium bromide4 mL of dimethyl sulfoxide. Heat 160 ° C in the presence of oxygenReaction for 24 hours. After the reaction was completed, distilled water was added to quench the reaction,Extraction with ethyl acetate 3 times, each time 10mL,The combined organic phases were concentrated to give 14.5 mg of 2-nitro-5-fluorobromobenzene,The yield is 33percent.

Reference： [1] Journal of Organic Chemistry, 2016, vol. 81, # 7, p. 2794 - 2803
[2] Patent: CN107325002, 2017, A, . Location in patent: Paragraph 0079

4
[ 1003-98-1 ]
[ 700-36-7 ]

Yield	Reaction Conditions	Operation in experiment
71%	With 3-chloro-benzenecarboperoxoic acid In 1,2-dichloro-ethane for 10 h; Reflux	General procedure: m-CPBA(1.7 g, 8.0 mmol, 85percent) was dissolved in 1,2-dichloroethane (15.0 mL) in a threeneckflask equipped with a condenser and heated to reflux (at rt in case of 1b).Then, the substrate aromatic amine (2.0 mmol) dissolved in 1,2-dichloroethane(5.0 mL) was added dropwise to the refluxing peracid solution. After 10 h, themixture was cooled to rt and quenched with saturated aqueous Na2S2O3. Thesolvent was removed under reduced pressure and the residue was treated with10percent NaOH solution followed by extraction with EtOAc. The combined extracts were washed with H2O and brine, dried over anhydrous Na2SO4. Removal of thesolvent under vacuum afforded the crude product, which was purified bycolumn chromatography using hexane/ethyl acetate as eluant.

Reference： [1] Bulletin de la Societe Chimique de France, 1995, vol. 132, p. 306 - 313
[2] Tetrahedron Letters, 2014, vol. 55, # 9, p. 1581 - 1584

5
[ 1073-06-9 ]
[ 700-36-7 ]

Reference： [1] European Journal of Organic Chemistry, 2006, # 13, p. 2956 - 2969
[2] Journal of Agricultural and Food Chemistry, 2009, vol. 57, # 17, p. 7912 - 7918
[3] Journal of Organic Chemistry, 1963, vol. 28, p. 1759 - 1762

6
[ 1073-06-9 ]
[ 700-36-7 ]
[ 321-23-3 ]

Reference： [1] Patent: US2010/280268, 2010, A1, . Location in patent: Page/Page column 22

7
[ 540-80-7 ]
[ 369-36-8 ]
[ 700-36-7 ]

Reference： [1] Patent: WO2014/12360, 2014, A1, . Location in patent: Paragraph 00424

8
[ 700-36-7 ]
[ 32338-02-6 ]

Reference： [1] Patent: WO2018/13774, 2018, A1,

9
[ 67-56-1 ]
[ 700-36-7 ]
[ 98447-30-4 ]

Yield	Reaction Conditions	Operation in experiment
68%	With tetrabutylammomium bromide; sodium hydroxide In dichloromethane; water at 25 - 40℃; for 16 h;	To a solution of 2-bromo-4-fluoro-1-nitro-benzene (60.0 g, 273 mmol, 1.00 eq) in the mixture of dichloromethane (400 mL) and methanol (440 mL) was added 1 M NaOH aqueous solution (1.00 L). Then a catalytic amount of TBAB (tetrabutylammonium bromide, 360 mg, 1.26 mmol) was added. The reaction was stirred at 40°C for 16 h. The reaction mixture was partitioned between DCM and water. Then the aqueous layer was extracted with dichloromethane (3 x 300 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel to give Compound 29 (43.1 g, 186 mmol, 68percent yield) as a yellow solid.‘H NMR: (400 MHz, Chloroform-d) 8.00 (d, J= 9.3 Hz, 1H), 7.23 (d, J 2.6 Hz, 1H), 6.93 (dd, J= 2.6, 9.3 Hz, 1H), 3.90 (s, 3H).

Reference： [1] Patent: WO2017/160569, 2017, A1, . Location in patent: Paragraph 00285; 00286
[2] Patent: WO2013/117645, 2013, A1, . Location in patent: Paragraph 00513

10
[ 700-36-7 ]
[ 124-41-4 ]
[ 98447-30-4 ]

Yield	Reaction Conditions	Operation in experiment
81%	at 20℃;	To a solution of 2-bromo-4-fluoro-1-nitrobenzene (2 g, 9.09 mmol) in THF (30 mL) was added sodium methoxide (1.48 g, 27 mmol). The mixture was stirred at roomtemperature overnight. Solvent was removed under vacuum and the residual was diluted with EtOAc, quenched with saturated ammonium chloride. The organic layer was washed with saturated sodium bicarbonate, brine, dried over sodium sulfate and concentrated. The crude product was purified with flash chromatography (loading in chloroform, 0percent to 50percent EtOAc in hexanes over 40 mm using a 120g silica gel cartridge).The desired fractions were combined and concentrated to yield Intermediate 103A (1.7 g,7.33 mmol, 81 percent yield) as an off-white solid. ‘H NMR (400MHz, chloroform-d) 8.00(d, J9.0 Hz, 1H), 7.23 (d, J=2.6 Hz, 1H), 6.93 (dd, J=9.0, 2.6 Hz, 1H), 3.90 (s, 3H).LC-MS: method C, RT = 1.82 mm, MS (ESI) m/z: 231.9 and 233.9 (M+H)t

Reference： [1] Patent: WO2018/13774, 2018, A1, . Location in patent: Page/Page column 469

11
[ 700-36-7 ]
[ 169674-02-6 ]

Reference： [1] European Journal of Organic Chemistry, 2006, # 13, p. 2956 - 2969

12
[ 700-36-7 ]
[ 1826-67-1 ]
[ 408355-23-7 ]

Reference： [1] European Journal of Organic Chemistry, 2006, # 13, p. 2956 - 2969
[2] Patent: WO2009/153307, 2009, A1, . Location in patent: Page/Page column 107
[3] Patent: US2010/29729, 2010, A1, . Location in patent: Page/Page column 51
[4] Patent: WO2008/104055, 2008, A1, . Location in patent: Page/Page column 31-32

[ 700-36-7 ] Synthesis Path-Downstream 1~66

1
[ 109-01-3 ]
[ 700-36-7 ]
[ 166818-85-5 ]

Yield	Reaction Conditions	Operation in experiment
87%	In ethanol; for 24h;Reflux;	To a rbf of 2-bromo-4-fluoro- 1 -nitrobenzene (2.49g, 11.36 mmol, 1 eq) in EtOH (30 mL) was added N-methylpiperazine (5.96 g, 56.82 mmol, 5 eq). The reaction was heated to reflux for 24 hours, after which the crude mixture was cooled, concentrated, adsorbed onto silica and purified on 40 g silica column (0-3% MeOH:DCM with 1% NH3) to yield l-(3-bromo-4-nitrophenyl)-4- methylpiperazine (2.95 g, 9.83 mmol, 87%). (0757) lU (CDCb): 8.03-7.99 (d, IH), 7.08-7.07 (m, IH), 6.79-6.75 (dd, IH), 3.42-3.39 (m, 4H), 2.56- 2.52 (m, 4H), 2.35 (s, 3H)
77%	In ethanol; at 0 - 60℃; for 4.5h;Product distribution / selectivity;	a) 1-(3-Bromo-4-nitro-phenyl)-4-methyl-piperazine To a cooled (0 C.) solution of 1.00 g (4.55 mmol) of <strong>[700-36-7]2-bromo-4-fluoronitrobenzene</strong> (Oakwood) in 12 mL of EtOH was added 1.52 mL (13.7 mmol) of piperidine. The solution was stirred at 0 C. for 0.5 h and then at 60 C. for 4 h. The mixture was concentrated in vacuo, dissolved in EtOAc (60 mL), washed with water (3*100 mL) and brine (100 mL), and dried (Na2SO4). Concentration in vacuo and chromatography on a 50-g silica SPE column with 1-3% MeOH- dichloromethane afforded 1.06 g (77%) of the title compound as a tannish yellow solid. Mass spectrum (ESI, m/z): Calcd. for C11H14BrN3O2, 300.0 (M+H, 79Br). found 300.1.
45%	at 60℃; for 1h;Product distribution / selectivity;	2-Bromo-4-fluoronitrobenzene (949 mg, 4.31 mmol) was added in two portions to neat N-methypiperazine (8 mL) at 0 C and allowed to warm to room temperature. The reaction was heated to 60 "C for 1 h, and then it was diluted with 50 mL of EtOAc and poured into H2O (50 mL). The layers were separated and the organic layer was washed with satd aq NaHCO3, dried (Na2SO4), and concentrated in vacuo to afford 580 mg (45 %) of the title compound as a yellow solid: Mass spectrum (ESI, m/z): Calcd. for CnHi4BrN3O2, 300.0 (M+H), found 300.1.

45%	at 0 - 60℃; for 1h;Neat (no solvent);Product distribution / selectivity;	2-Bromo-4-fluoronitrobenzene (949 mg, 4.31 mmol) was added in two portions to neat N-methypiperazine (8 mL) at 0 C. and allowed to warm to room temperature. The reaction was heated to 60 C. for 1 h, and then it was diluted with 50 mL of EtOAc and poured into H2O (50 mL). The layers were separated and the organic layer was washed with satd aq NaHCO3, dried (Na2SO4), and concentrated in vacuo to afford 580 mg (45%) of the title compound as a yellow solid: Mass spectrum (ESI, m/z): Calcd. for C11H14BrN3O2, 300.0 (M+H), found 300.1.
45%	at 0 - 60℃; for 1h;Neat liquid(s);Product distribution / selectivity;	a) 1-(3-Bromo-4-nitro-phenyl)-4-methyl-piperazine 2-Bromo-4-fluoronitrobenzene (949 mg, 4.31 mmol) was added in two portions to neat N-methypiperazine (8 mL) at 0 C. and allowed to warm to room temperature. The reaction was heated to 60 C. for 1 h, and then it was diluted with 50 mL of EtOAc and poured into H2O (50 mL). The layers were separated and the organic layer was washed with satd aq NaHCO3, dried (Na2SO4), and concentrated in vacuo to afford 580 mg (45%) of the title compound as a yellow solid: Mass spectrum (ESI, m/z): Calcd. for C11H14BrN3O2, 300.0 (M+H). found 300.1.
45%	at 0 - 60℃; for 1h;Neat (no solvent);Product distribution / selectivity;	2-Bromo-4-fluoronitrobenzene (949 mg, 4.31 mmol) was added in two portions to neat N-methypiperazine (8 mL) at 0 C and allowed to warm to room temperature. The reaction was heated to 60 C for 1 h, and then it was diluted with 50 mL of EtOAc and poured into H2O (50 mL). The layers were separated and the organic layer was washed with satd aq NaHCO3, dried (Na2SO4), and concentrated in vacuo to afford 580 mg (45 %) of the title compound as a yellow solid: Mass spectrum (ESI, m/z): Calcd. for C11Hi4BrN3O2, 300.0 (M+H), found 300.1.

Reference： [1]Bulletin de la Societe Chimique de France,1995,vol. 132,p. 306 - 313
[2]Patent: WO2018/106667,2018,A1 .Location in patent: Page/Page column 102
[3]Patent: US2008/51402,2008,A1 .Location in patent: Page/Page column 38
[4]Patent: WO2006/47277,2006,A2 .Location in patent: Page/Page column 43
[5]Patent: US2006/281788,2006,A1 .Location in patent: Page/Page column 48
[6]Patent: US2008/51402,2008,A1 .Location in patent: Page/Page column 34
[7]Patent: WO2007/48088,2007,A2 .Location in patent: Page/Page column 61

2
[ 1003-98-1 ]
[ 700-36-7 ]

Yield	Reaction Conditions	Operation in experiment
71%	With 3-chloro-benzenecarboperoxoic acid; In 1,2-dichloro-ethane; for 10h;Reflux;	General procedure: m-CPBA(1.7 g, 8.0 mmol, 85%) was dissolved in 1,2-dichloroethane (15.0 mL) in a threeneckflask equipped with a condenser and heated to reflux (at rt in case of 1b).Then, the substrate aromatic amine (2.0 mmol) dissolved in 1,2-dichloroethane(5.0 mL) was added dropwise to the refluxing peracid solution. After 10 h, themixture was cooled to rt and quenched with saturated aqueous Na2S2O3. Thesolvent was removed under reduced pressure and the residue was treated with10% NaOH solution followed by extraction with EtOAc. The combined extracts were washed with H2O and brine, dried over anhydrous Na2SO4. Removal of thesolvent under vacuum afforded the crude product, which was purified bycolumn chromatography using hexane/ethyl acetate as eluant.
33%		(2) Diazo on the nitro group:To the reaction vessel was added 420 g of 2-bromo-4-fluoroaniline and 1000 mL of fluoroboric acid in the first step.Stir, cool the ice brine bath, add 240 g of sodium nitrite in batches, and control the temperature below 10 during the feeding process.After the addition is completed, stir for a while, suction filtration, and filter cake for use. Add 32 g of copper powder to another reaction flask and add a solution of 2400 g of sodium nitrite and 5400 mL of water.Stir and control the temperature at about 35 degrees. Add the above filter cake in batches. After the addition, stir for a while.Acidification, extraction, rotary steaming, crystallization,The yield of 2-bromo-4-fluoronitrobenzene was 160.4 g, and the content was more than 98%, and the yield was 33%.

Reference： [1]Bulletin de la Societe Chimique de France,1995,vol. 132,p. 306 - 313
[2]Tetrahedron Letters,2014,vol. 55,p. 1581 - 1584
[3]Patent: CN109369411,2019,A .Location in patent: Paragraph 0009-0011; 0013-0015

3
[ 700-36-7 ]
[ 75-31-0 ]
[ 131885-33-1 ]

Yield	Reaction Conditions	Operation in experiment
	at 150℃; for 36h;

Reference： [1]Jacobsen, E. Jon; Stelzer, Lindsay S.; Belonga, Kenneth L.; Carter, Donald B.; Im, Wha Bin; Sethy, Vimala H.; Tang, Andrew H.; Von Voigtlander, Philip F.; Petke, James D. [Journal of Medicinal Chemistry, 1996, vol. 39, # 19, p. 3820 - 3836]

4
[ 700-36-7 ]
[ 1826-67-1 ]
[ 408355-23-7 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; at -78 - 20℃;	Description for D131; 7-Bromo-5-fluoro-1 H-indole (D131); To a solution of 2-bromo-4-fluoro-1 -nitrobenzene (24 g) in anhydrous THF (200 ml.) was added 1 M vinylmagnesium bromide in THF (328 ml.) dropwise at -78 0C slowly, then the mixture was allowed to warm to RT and stirred for 2 hours. TLC indicated the reaction was complete. The reaction mixture was poured into saturated aqueousNH4CI solution. The organic phase was separated by extraction with EA (3 x 200 ml_). The crude product was purified by column chromatography to afford 7-bromo-5- fluoro-1 H-indole (D131 ) (15 g) as a brown oil.
		Description for D131; 7-Bromo-5-fluoro-1H-indole (D131); To a solution of 2-bromo-4-fluoro-1-nitrobenzene (24 g) in anhydrous THF (200 mL) was added 1 M vinylmagnesium bromide in THF (328 mL) dropwise at -78 C. slowly, then the mixture was allowed to warm to RT and stirred for 2 hours. TLC indicated the reaction was complete. The reaction mixture was poured into saturated aqueous NH4Cl solution. The organic phase was separated by extraction with EA (3×200 mL). The crude product was purified by column chromatography to afford 7-bromo-5-fluoro-1H-indole (D131) (15 g) as a brown oil.
		EXAMPLE 4Potassium 4- {.-[({ 5-fluoro-l-[4-(trifluoromethyl)benzyl]- IH- indol-7- yl } carbonyl)amino] cyclopropyl } benzoate <n="33"/>Step 1 : 7-bromo-5-fluoro-l //-indole2-bromo-4-fluoro-l -nitrobenzene (3.5 g, 15.9 mmol) was dissolved in anhydrous THF (160 ml) under N2. The reaction was cooled to -450C and vinyl magnesium bromide (3 eq, IM) was added, the mixture was stirred for 30 min at this temperature. The reaction was quenched with NH4Cl (sat.) and IN HCl. The aqueous layer was then extracted 3x with ether. The combined organic layers were washed with water and brine, dried over MgSO4, filtered and then concentrated under reduced pressure. The product was purified by flash chromatography on silica gel. 1H NMR (500 MHz, DMSO-d6): delta 11.45 (bs, IH), 7.50 (t, IH), 7.40 (dd, IH), 7.25 (dd, IH), 6.50 (dd, IH).

Reference： [1]European Journal of Organic Chemistry,2006,p. 2956 - 2969
[2]Patent: WO2009/153307,2009,A1 .Location in patent: Page/Page column 107
[3]Patent: US2010/29729,2010,A1 .Location in patent: Page/Page column 51
[4]Patent: WO2008/104055,2008,A1 .Location in patent: Page/Page column 31-32

5
[ 700-36-7 ]
[ 954124-99-3 ]
2-(3-bromo-4-nitro-phenyl)-malonic acid dimethyl ester; enol form [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a suspension of NaH (364 mg, 9.08 mmol) in 10 mL of DMF at 0 C. was added malonic acid dimethyl ester (519 muL, 4.54 mmol). The resulting mixture was warmed to RT and stirred for 0.5 h under Ar. 2-Bromo-4-fluoro-1-nitro-benzene (500 mg, 2.27 mmol) was added to the mixture and the reaction was stirred at RT for 16 h under Ar. The mixture was then treated with 2 mL of satd aq NH4Cl followed by 10 mL of H2O and extracted with DCM (3×10 mL). The combined extracts were washed with water (10 mL), brine (5 mL) and dried (Na2SO4). Removal of the solvent in vacuo followed by flash chromatography of the residue on silica gel (1:4 hexane-DCM) gave 604 mg (80%) of a yellow-green oil containing the pure title compound as a mixture of di-ester (A) and its enol tautomer (B): 1H-NMR (CDCl3; 400 MHz): A: delta 8.48 (d, 1H, J=2.5 Hz), 8.21 (dd, 1H, J=8.8, 2.5 Hz), 7.85 (d, 1H, J=8.8 Hz), 5.34 (s, 1H), 3.81 (s, 6H). B: delta 7.85 (d, 1H, J=8.4 Hz), 7.82 (d, 1H, J=1.9 Hz), 7.54 (dd, 1H, J=8.4, 1.9 Hz), 4.68 (s, 1H), 3.80 (s, 6H).
		a) 2-(3-Bromo-4-nitro-phenyl)-malonic acid dimethyl ester To a suspension of NaH (364 mg, 9.08 mmol) in 10 mL of DMF at 0 C. was added malonic acid dimethyl ester (519 muL, 4.54 mmol). The resulting mixture was warmed to RT and stirred for 0.5 h under Ar. 2-Bromo-4-fluoro-1-nitro-benzene (500 mg, 2.27 mmol) was added to the mixture and the reaction was stirred at RT for 16 h under Ar. The mixture was then treated with 2 mL of satd aq NH4Cl followed by 10 mL of H2O and extracted with DCM (3*10 mL). The combined extracts were washed with water (10 mL), brine (5 mL) and dried (Na2SO4). Removal of the solvent in vacuo followed by flash chromatography of the residue on silica gel (1:4 hexane-DCM) gave 604 mg (80%) of a yellow-green oil containing the pure title compound as a mixture of di-ester (A) and its enol tautomer (B): 1H-NMR (CD3OD; 400 MHz): A: delta 8.48 (d, 1H, J=2.5 Hz), 8.21 (dd, 1H, J=8.8, 2.5 Hz), 7.85 (d, 1H, J=8.8 Hz), 5.34 (s, 1H), 3.81 (s, 6H). B: delta 7.85 (d, 1H, J=8.4 Hz), 7.82 (d, 1H, J=1.9 Hz), 7.54 (dd, 1H, J=8.4, 1.9 Hz), 4.68 (s, 1H), 3.80 (s, 6H).

Reference： [1]Patent: US2007/249649,2007,A1 .Location in patent: Page/Page column 41-42
[2]Patent: US2007/249593,2007,A1 .Location in patent: Page/Page column 41

6
[ 700-36-7 ]
[ 175278-00-9 ]
[ 175676-49-0 ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 6905 - 6917

7
[ 700-36-7 ]
[ 169674-02-6 ]

Reference： [1]European Journal of Organic Chemistry,2006,p. 2956 - 2969

8
[ 700-36-7 ]
[ 68716-47-2 ]
[ 686338-59-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; benzene; at 75℃;	The mixture containing 1-BROMO 5-fluoro 2-NITROBENZENE (1 g, 4.5 mmol), 2,4-dichloro benzeneboronicacid (907 mg, 4.7 mmol), sodiumcarbonate (1.44 g, 13.5 mmol) in benzene and 3 ml of water was purged with nitrogen for 30 mins. <P>TETRAKIS (TRIPHENYLPHOSPHINE) -PALLADIUM (0) (264 MGS, 0.2 MMOL) WAS ADDED TO THE mixture and was heated to 75C overnight. The reaction mixture was partitioned between ethyl acetate and water. Organic layer was separated and washed with brine, dried (MGSO4), filtered and concentrated in vacuo to give a brown solid which was recrystallized to give IG (yield, 80%) of white solid. The product gave satisfactory NMR. HPLC: 13. 2min (100%) MS (M+H/Z), 266

Reference： [1]Patent: WO2004/37791,2004,A1 .Location in patent: Page 39

9
[ 700-36-7 ]
[ 57279-69-3 ]

Yield	Reaction Conditions	Operation in experiment
88%		ABSOLUTE ETOH (700 ml) is cooled in an ice bath and sodium (5.2 g) is slowly added. The cooling bath is removed and the resulting mixture allowed to stir at RT for 2 hours. 2-Bromo-4-fluoro-1-nitrobenzene (15.0 g) is slowly added, and the resulting mixture is allowed to stir for 15 hours. A solution of citric acid (1.0 M) is added until the pH IS # 4. Water (200 ml) is added, the volatiles are removed ILL vacuo and the residue is taken up in EtOAc, washed with water (2 x 100 ml) and then brine, dried (MgSO4), and crystallized from 1-chlorobutane/n-hexane to give 2-bromo-4- ETHOXY-1-NITROBENZENE. Yield 88%. 1H NMR (400 MHz, DMSO-d6) 8 8.04, 7.40, 7.11, 4. 15, 1.33.

Reference： [1]Patent: WO2004/85433,2004,A2 .Location in patent: Page 64

10
[ 700-36-7 ]
[ 105-13-5 ]
[ 929095-68-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate; In dichloromethane; water; for 8h;	2-Bromo-4-fluoro-1 -nitrobenzene (20.0 g, 90.9 mmol) and 4-methoxybenzyl alcohol (22.7 mL, 182 mmol) were dissolved in DCM (400 ml_) with stirring. 1 N sodium hydroxide solution (400 mL) was added followed by tetrabutylammonium hydrogensulfate (3.09 g, 9.10 mmol). The reaction was stirred for 8 h and poured into a separatory funnel. The layers were separated and the aqueous was extracted once with DCM and once with diethyl ether. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash chromatography afforded 28.01 g (91%) of the title compound. 1H NMR (400 MHz, CDCI3): delta 8.03 (d, 1H, J= 9.2 Hz), 7.50 (d, 1H, J= 2.6 Hz), 7.39-7.34 (m, 2H), 7.17 (dd, 1H, J= 2.7, 9.0 Hz), 6.95-6.91 (m, 2H), 5.14 (s, 2H), 3.73 (s, 3H).
91%	With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate; In dichloromethane; water; at 20℃; for 8h;	2-bromo-4-fluoro-1 -nitrobenzene (20.0 g, 90.9 mmol) and 4-methoxybenzyl alcohol (22.7 ml_, 182 mmol) were dissolved in dichloromethane (400 mL) with stirring. 1 N sodium hydroxide solution (400 mL) was added followed by tetrabutylammonium hydrogensulfate (3.09 g, 9.10 mmol). The reaction was stirred for 8 h and poured into a separatory funnel. The layers were separated and the aqueous was extracted once with dichloromethane and once with diethyl ether. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by flash EPO <DP n="67"/>chromatography afforded 28.01 g (91%) of the title compound. 1H NMR (400 MHz, CDCI3): delta 8.03 (d, 1 H1 J= 9.2 Hz), 7.50 (d, 1 H, J= 2.6 Hz)1 7.39-7.34 (m, 2H), 7.17 (dd, 1H, J= 2.7, 9.0 Hz), 6.95-6.91 (m, 2H), 5.14 (s, 2H), 3.73 (s, 3H).
	With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide; In dichloromethane; for 24h;	l-Bromo-5-fluoro-2-nitrobenzene (3 g, 13.6 mmol), 4-methoxybenzyl alcohol (3.4 mL, 27.3 mmol) and tetrabutylammonium hydrogen sulfate (462 mg, 1.36 mmol) were stirred vigorously in NaOH (1 M aqueous solution, 60 mL) and DCM (60 mL) for 1 d. The layers were separated and the aqueous was extracted with DCM. The combined organics were dried (hydrophobic frit) and concentrated in vacuo. The residue was purified by column chromatography using silica gel and eluting with DCM. The fractions containing product were combined and concentrated in vacuo to give the desired compound. NMR delta (ppm)(DMSO-d6): 8.08 (1 H, dd, ArH), 7.53 (1 H, d, ArH), 7.44-7.36 (2 H, m, ArH), 7.28- 7.17 (1 H, m, ArH), 6.99-6.94 (2 H, m, ArH), 5.18 (2 H, s, CH2), 3.77 (3 H, s, CH3).

Reference： [1]Tetrahedron Letters,2008,vol. 49,p. 6348 - 6351
[2]Patent: WO2007/30361,2007,A2 .Location in patent: Page/Page column 74
[3]Patent: WO2007/30366,2007,A1 .Location in patent: Page/Page column 65-66
[4]Patent: WO2013/117645,2013,A1 .Location in patent: Paragraph 00327

11
[ 371-40-4 ]
[ 700-36-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-Bromosuccinimide; In dichloromethane; at 0 - 20℃;	To a solution of 4-fluoroaniline (20 g, 180 mmol) in dichloromethane (100 mL) at 0 C. was added N-bromosuccinimide (34 g, 180 mmol, in 60 mL dichloromethane) dropwise. The mixture was stirred at room temperature overnight. The reaction was washed with saturated sodium sulfite, saturated sodium bicarbonate, and brine and concentrated to provide the title compound (34 g, 154.5 mmol, 100%). 1H NMR (400 MHz, CDCl3) delta ppm 7.12-7.21 (m, 1H), 7.47 (dd, J=7.60, J=2.40, 1H), (dd, J=9.60, J=6.40, 1H).

Reference： [1]Patent: US2008/300242,2008,A1 .Location in patent: Page/Page column 62
[2]Patent: CN109369411,2019,A

12
[ 4433-63-0 ]
[ 700-36-7 ]
[ 1089279-29-7 ]

Yield	Reaction Conditions	Operation in experiment
24%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 100℃;	2-Bromo-4-fluoro-1-nitrobenzene (21.8 g, 100 mmol), <strong>[4433-63-0]ethyl boronic acid</strong> (7.5 g, 100 mL), K2CO3 (40 g, 300 mL), dichloro[1,1'-bis(diphenylphosphino)-ferrocene]palladium (II) (6 g) in dioxane (250 mL) and H2O (80 mL) was flushed with N2 and heated at 100 C. overnight. The reaction was diluted with EtOAc and H2O and filtered through Celite. The organic layer was separated, concentrated and purification by flash chromatography provided the title compound (4.1 g, 24.2 mmol, 24%). 1H NMR (400 MHz, CDCl3) delta ppm 1.30 (t, J=7.78, 3H), 2.92 (q, J=7.78, 2H), 7.01-7.11 (m, 2H), 7.98 (dd, J=8.53 Hz, J=5.53 Hz, 1H).
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 24h;Inert atmosphere;	2-Bromo-4-fluoro-l -nitrobenzene (1.63 g, 7.4 mmol), <strong>[4433-63-0]ethylboronic acid</strong> (0.6 g, 8.14 mmol), potassium carbonate (3.1 g, 22.2 mmol) and [l,l'-bis(diphenylphosphino)ferrocene]- dichloropalladium(II) (302 mg, 0.37 mmol) were suspended in dioxane (25 mL) and water (5 mL). The stirred reaction mixture was degassed (N2 (g)) and heated to 100 C for 1 d. The reaction mixture was filtered through celite and partitioned between EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc, the organics were combined, dried (MgSO i) and concentrated in vacuo. The resulting residue was purified by column chromatography using silica gel and eluting with 0-50% EtOAc in isohexanes to give the desired compound.
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Inert atmosphere;	2-Bromo-4-fluoro-l -nitrobenzene (1.63 g, 7.4 rnrnol), <strong>[4433-63-0]ethylboronic acid</strong> (0.6 g, 8.14 rnrnol), potassium carbonate (3.1 g, 22.2 mmol) and [1,1 '- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (302 mg, 0.37 mmol) were suspended in dioxane (25 mL) and water (5 mL). The stirred reaction mixture was degassed (N2) and heated to 100C for 1 d. The reaction mixture was filtered through Celite and partitioned between EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc, the organics were combined, dried (MgSO i) and concentrated in vacuo. The resulting residue was purified by column chromatography using silica gel and eluting with 0-50% EtOAc in isohexanes to give the desired compound.

Reference： [1]Patent: US2008/300242,2008,A1 .Location in patent: Page/Page column 62
[2]Patent: WO2013/117649,2013,A1 .Location in patent: Paragraph 00297
[3]Patent: WO2013/117645,2013,A1 .Location in patent: Paragraph 00403

13
[ 700-36-7 ]
[ 103-84-4 ]
[ 1095715-30-2 ]

Yield	Reaction Conditions	Operation in experiment
66%		The title compound was prepared with the analogous procedure described in example 3 using 1-Bromo-5-fluoro-2-nitrobenzene and lambda/-phenylacetamide (81 mg, 0.6 mmol) as starting materials to yield the title compound as brown solid (75 mg, 66%). 1H NMR (DMSO) delta 2.50 (s, 3 H), 7.11 (d, 1 H), 7.21-7.29 (m, 1 H), 7.59-7.69 (m, 5 H), 7.79 (br s, 1 H).

Reference： [1]Patent: WO2009/413,2008,A1 .Location in patent: Page/Page column 35

14
[ 700-36-7 ]
[ 7486-35-3 ]
[ 951667-82-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	tetrakis(triphenylphosphine) palladium(0); In toluene; at 20℃; for 67h;Inert atmosphere; Reflux;	At RT and under Argon, Pd(PPh3)4 (67 mg, 0.058 mmol) was added to a solution of <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (391 mg, 1.77 mmol) and tributyl(vinyl)tin (620 mg, 1.96 mmol) in toluene (degassed by purging, 10 mL). The reaction was stirred at reflux for 7 hours and then at RT for 60 hours. The reaction mixture was evaporated to dryness in vacuo. The residue was dissolved in CH2Cl2 (100 mL) and washed with aq. sat. NaHCO3 (50 mL). The aqueous-layer was extracted once more with CH2Cl2 (50 mL). The DCM-extracts were dried (Na2SO4), filtered, and evaporated to dryness in vacuo. The crude product was purified by column chromatography (heptane to EtOAc/heptane: 1/4) to obtain 4-fluoro-1-nitro-2-vinylbenzene as a yellow oil (266 mg, 89%, purity (LC) n.d.)NMR: 1H (CDCl3): delta 8.04 (dd, J=5.04 Hz and J=8.04 Hz, 1H), 7.29 (dd, J=2.52 Hz and J=9.08 Hz, 1H), 7.22 (ddd, J=1.00 Hz and J=10.8 Hz and J=17.2 Hz, 1H), 7.10 (ddd, J=2.76 Hz and J=7.08 Hz and J=9.08 Hz, 1H), 5.76 (d, J=17.2 Hz, 1H), 5.55 (d, J=10.8 Hz, 1H).
	With tetrakis(triphenylphosphine) palladium(0); In toluene; at 20 - 90℃; for 72h;Inert atmosphere;	Step1: Stirred solution of <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (5.0 g, 22.52 mmol, 1 eq) in toluene (110 mL) was degassed with Ar for 20 min. To the above solution tertiary butyl vinyl tin (7.8 g, 24.77 mmol, 1.1 eq) and Pd(PPli3)4 (0.832 ml, 0.72 mmol, 0.05 eq) was added, then stirred for 48 h at 90C and 2 4h at RT . The solvent was evaporated and residue was dissolved in EtOAc (500 mL). Organic layer was washed with water and then with brine (100 mL).The organic layer was dried over Na2S04, concentrated under reduced pressure to get the crude material which purified by column chromatography (230-400 mesh silica gel; 5% EtOAc/hexane; R^value-0.4) to afford 4-fluoro-1-nitro-2-vinylbenzene (3.5 g, 93%) as brown solid which still includes some tine reagents and starting material (were not removed completely).

Reference： [1]Tetrahedron Letters,2009,vol. 50,p. 386 - 388
[2]Patent: US2010/280268,2010,A1 .Location in patent: Page/Page column 53
[3]Patent: WO2020/16453,2020,A1 .Location in patent: Page/Page column 66-67

15
[ 64-17-5 ]
[ 700-36-7 ]
[ 57279-69-3 ]

Yield	Reaction Conditions	Operation in experiment
68%		Absolute ETOH (300mL) is cooled in an ice bath and sodium (2.1 g) is slowly added. The cooling bath is removed and the resulting mixture allowed to stir at ambient temperature for 2 hours. 2-BROMO-4-FLUORO-1-NITROBENZENE (6.0 g) is slowly added, and the resulting mixture allowed to stir for 15 hours. A solution of citric acid (1.0 M) is added until the pH was-4. Water is added, the volatiles are removed in vacuo and the residue taken up in EtOAc, washed with water, brine, dried (NA2S04)- and 2-BROMO-4-ETHOXY-1-NITROBENZENE is crystallized from 1-CHLOROBUTANE/HEXANE. YIELD 68%. 1H NMR (400 MHz, DMSO-d6) # 8. 04,7. 40,7. 11, 4.15, 1.33.

Reference： [1]Patent: WO2004/85433,2004,A2 .Location in patent: Page 57

16
[ 700-36-7 ]
[ 27514-07-4 ]
[ 1223105-27-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium carbonate; In dimethyl sulfoxide; at 80℃; for 24h;	Preparation of 7-(3-bromo-4-nitrophenyl)-7-azabicydo[2.2.1]heptane (2S). To a solution of 2-bromo-4-fluoro-l-nitro-benzene 24 (1.1 g, 4.8 mmol) and K2CO3 (2.0 g, 14.3 mmol) in DMSO (8.400 rnL) was added 7-azabicyclo[2.2.1]heptane 7a (765.4 mg, 5.7 mmol) portion-wise. The reaction was stirred at 80 0C for 24 h. The reaction was diluted with water to precipitate the product. The solid was redissolved in dichloromethane, washed with 1.0 N HCl, dried over MgSO4, filtered and concentrated to provide 7-(3-bromo-4-nitxophenyl)-7- azabicyclo[2.2.1]heptane 25 (1.1 g, 78% yield). The crude product was used directly in the next step. IJCMS m/z 299.1 [M+H]+, retention time 1.97 min (RP-C18, 10-99% CH3CN/0.05% TFA over 3 min).

Reference： [1]Patent: WO2010/48526,2010,A2 .Location in patent: Page/Page column 48

17
[ 279-40-3 ]
[ 700-36-7 ]
[ 1223105-27-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	In dimethyl sulfoxide; at 80℃;	To a solution of <strong>[700-36-7]2-bromo-4-fluoro-1-nitro-benzene</strong> (250 mg, 1.14 mmol) in DMSO (2 mL) was added 7-azabicyclo[2.2.1]heptane (182 mg, 1.36 mmol) portion-wise. The reaction was stirred at 80 C. for 24 h. The reaction was quenched with water and the aqueous layer was extracted with dichloromethane. The combined organic extracts were washed with 1 N HCl, dried over MgSO4, filtered and concentrated in vacuo to provide 7-(3-bromo-4-nitrophenyl)-7-azabicyclo[2.2.1]heptane (864 mg, 98% yield). LC/MS m/z 298.5 [M+H]+

Reference： [1]Patent: US2010/168094,2010,A1 .Location in patent: Page/Page column 67; 68

18
[ 7223-38-3 ]
[ 700-36-7 ]
[ 1233531-21-9 ]

Yield	Reaction Conditions	Operation in experiment
68%	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In N,N-dimethyl-formamide; at 60℃; for 5h;Inert atmosphere;	To a flask charged with N,N-dimethylprop-2-yn-1-amine (737 mg, 945 muL, 8.86 mmol), <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (1300 mg, 5.91 mmol), PdCl2(PPh3)2 (415 mg, 0.59 mmol), CuI (169 mg, 0.89 mmol) were added triethylamine (2.47 mL, 17.73 mmol) and DMF (10 mL) under N2 atmosphere. The reaction mixture was heated at 60 C. for 5 h, then poured into water (300 mL) and extracted with ethyl acetate (3*40 mL). The organic fractions were combined, dried over MgSO4, filtered, and concentrated in vacuo. Purification by silica gel chromatography (50-100% ethyl acetate/hexanes) yielded 3-(4-fluoro-2-nitrophenyl)-N,N-dimethylprop-2-yn-1-amine (895 mg, 68% yield). LC/MS m/z 223.0 [M+H]+

Reference： [1]Patent: US2010/168094,2010,A1 .Location in patent: Page/Page column 61; 62

19
[ 42726-73-8 ]
[ 700-36-7 ]
[ 594844-44-7 ]

Yield	Reaction Conditions	Operation in experiment
		Sodium hydride (60percent in mineral oil; 0.985 g) is suspended in N,N-dimehylforamamide (20 mL), and to this suspension was added dropwise a solution of tert-butyl methyl malonic acid ester (4.29 g) in N,N-dimethylformamide (5 mL) under ice-cooling. After completion of the foam generation, a solution of 2-bromo-4-fluoro-1-nitrobenzene (2.71 g) in N,N-dimethylformamide (5 mL) was dropwise added thereto at the same temperature, and the mixture was stirred at 60°C for 3 hours. The reaction mixture was concentrated, neutralized with 1N hydrochloric acid, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:4 to 5) to give the title compound (7.54 g) as an oil.

Reference： [1]Patent: EP1669345,2006,A1 .Location in patent: Page/Page column 87

20
[ 107-98-2 ]
[ 700-36-7 ]
[ 943247-79-8 ]

Yield	Reaction Conditions	Operation in experiment
100%		Example 35: 5-(2-Methoxy-l -methylethoxy)-N-l ,3-thiazol-2-yl-lH-indazol-3-amine[0372] To a stirred suspension of sodium hydride (60% oil dispersion, 1.36 g, 34.1 mraol) in DMF (50 mL) was added l-methoxy-2-propanol (3.4 mL, 34.1 mmol) at 00C, and the mixture was stirred for 30 min at 00C. To the mixture was added a solution of l-bromo-5- fluoro-2-nitrobenzene (5.0 g, 22.7 mmol) in DMF (10 mL) at 00C, and the mixture was stirred for 1 h at room temperature. To the mixture was carefully added IN HCl (50 mL) at 00C. The aqueous layer was extracted with EtOAc, and the organic layer was washed with IN HCl, H2O, and brine, dried (MgSO4), filtered, and concentrated in vacuo to give 6.60 g of 2-bromo-4-(2-methoxy-] -methylethoxy)-l -nitrobenzene (compound 35A) as a light yellow oil, which was used for the next step without further purification. 1H NMR (300 MHz, CDCl3) delta 1.34 (d, 3H, 7=6.40 Hz) 3.40 (s, 3H) 3.47 - 3.62 (m, 2H) 4.57 - 4.71 (m, IH) 6.94 (dd, IH, 7=9.23, 2.64 Hz) 7.25 - 7.28 (m, IH) 7.97 (d, IH, 7=9.23 Hz). [0373] To a stirred solution of 2-bromo-4-(2-methoxy-l-methylethoxy)-l -nitrobenzene (2.007 g, 6.92 mmol) in l-methyl-2-pyrrolidinone (20 mL) was added copper cyanide (0.75 g, 8.3 mmol) at room temperature. The mixture was stirred for 30 min at 1500C. After cooling, the mixture was diluted with EtOAc. The organic layer was washed successively with H2O, IN HCl, H2O, and brine, dried (MgSO4), filtered, and concentrated in vacuo. Purification by silica gel chromatography (hexane:EtOAc=30:l to 10:1 to 5:1 to 3:1) gave 1.46 g (89%) of 5- (2-methoxy-l-methylethoxy)-2-nitrobenzonitrile (compound 35B) as a brown oil. 1H NMR <n="124"/>(300 MHz, CDCl3) delta 1.37 (d, 3H, 7=6.40 Hz) 3.39 (s, 3H) 3.49 - 3.66 (m, 2H) 4.63 - 4.81 (m, IH) 7.24 (dd, IH, 7=9.42, 2.83 Hz) 7.37 (d, IH, 7=2.83 Hz) 8.28 (d, IH, 7=9.23 Hz). MS (ES) [m+H] calc'd for CnHi2N2O4, 237; found 237.[0374] 2-Amino-5-(2-methoxy-l-methylethoxy)benzonitxile (compound 35C) was prepared in 49% yield from 5-(2-methoxy-l-methylethoxy)-2-nitrobenzonitrile according to a procedure analogous to that outlined in Example 34. 1H NMR (300 MHz, CDCl3) delta 1.26 (d, 3H, 7=6.22 Hz) 3.40 (s, 3H) 3.42 - 3.57 (m, 2H) 4.13 (s, 2H) 4.27 - 4.40 (m, IH) 6.68 (d, IH, 7=8.85 Hz) 6.95 (d, IH, 7=2.83 Hz) 6.98 - 7.05 (m, IH). MS (ES) [m+H] calc'd for CnH14N2O2, 207; found 207.[0375] 5-(2-Methoxy-l-methylethoxy)-lH-indazol-3-amine (compound 35C) was prepared in 87% yield from 2-amino-5-(2-methoxy-l -methylethoxy)benzonitrile according to a procedure analogous to that outlined in Example 28. 1H NMR (300 MHz, DMSO-^6) delta 1.22 (d, 3H, 7=6.22 Hz) 3.30 (s, 3H) 3.40 - 3.55 (m, 2H) 4.35 - 4.54 (m, IH) 5.16 (s, 2H) 6.88 (dd, IH, 7=8.85, 2.45 Hz) 7.12 (d, IH, 7=8.85 Hz) 7.22 (d, IH, 7=2.26 Hz) 11.16 (s, IH). MS (ES) [m+H] calc'd for C11H13N3O2, 222; found 222.[0376] iV-[5-(2-Methoxy-l -methylethoxy)-l H-indazol-3-yl]thiourea (compound 35E) was prepared in 68% yield from 5-(2-methoxy-l-methylethoxy)-lH-indazol-3-amine according to a procedure analogous to that outlined in Example 9. 1H NMR (300 MHz, DMSO-^6) delta 1.27 (d, 3H, 7=6.22 Hz) 3.31 (s, 3H) 3.42 - 3.60 (m, 2H) 4.40 - 4.61 (m, IH) 7.01 (dd, IH, 7=8.95, 2.35 Hz) 7.33 (d, IH, 7=8.85 Hz) 7.77 (d, IH, 7=2.07 Hz) 8.68 (brs, IH) 9.27 (brs, IH) 10.70 (s, IH) 12.48 (s, IH). MS (ES) [m+H] calc'd for C12Hi6N4O2S, 281 ; found 281. [0377] The title compound was prepared in 49% yield from lambda/'-[5-(2-methoxy-l- methylethoxy)-lH-indazol-3-yl]thiourea according to a procedure analogous to that outlined in Example 28. 1H NMR (300 MHz, DMSO-J6) delta 1.27 (d, 3H, 7=6.44 Hz) 3.31 (s, 3H) 3.39 - 3.65 (m, 2H) 4.36 - 4.59 (m, IH) 6.96 (d, IH, 7=3.41 Hz) 7.00 (dd, IH, 7=9.09, 2.27 Hz) 7.30 (d, IH, 7=9.09 Hz) 7.34 (d, IH77=3.41 Hz) 7.66 (d, IH, 7=1.89 Hz) 11.10 (s, IH) 12.13 (s, IH). MS (ES) [m+H] calc'd for C14H16N4O2S, 305; found 305.

Reference： [1]Patent: WO2007/75847,2007,A2 .Location in patent: Page/Page column 122-123

21
[ 700-36-7 ]
[ 100-46-9 ]
[ 131885-34-2 ]

Yield	Reaction Conditions	Operation in experiment
86%		Under Argon and at RT, Pd(OAc)2 (32 mg, 0.14 mmol) and BINAP (90 mg, 0.14 mmol) were added to a solution of benzylamine (225 mg, 2.10 mmol) and 4-fluoro-2-bromonitrobenzene (463 mg, 2.10 mmol) in toluene (degassed by purging, 5 mL). The reaction mixture was heated at 100 C. for 3 minutes and then cooled to 0 C. Upon addition of sodium tert-butoxide (253 mg, 2.63 mmol) the reaction mixture turned red. The reaction was stirred at 70 C. for 24 hours and then at RT for 48 hours. The reaction was filtered over Kiezelguhr. Residue was rinsed with EtOAc. The filtrate was evaporated to dryness in vacuo. The crude product was purified by flash column chromatography to afford N1-benzyl-5-fluoro-2-nitroaniline as a yellow crystalline compound (440 mg, 86%, purity (LC) n.d.).NMR: 1H (CDCl3): delta 8.55 (bs, 1H), 8.24 (dd, J=6.04 Hz and J=9.32 Hz, 1H), 7.42-7.30 (m, 5H), 6.46 (dd, J=2.52 Hz and J=11.4 Hz, 1H), 6.39 (ddd, J=2.52 Hz and J=7.32 Hz and J=9.60 Hz, 1H), 2.12 (s, 2H).

Reference： [1]Patent: US2010/280268,2010,A1 .Location in patent: Page/Page column 17

22
[ 700-36-7 ]
[ 98-80-6 ]
[ 1478-01-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate; In ethanol; water; toluene; for 6h;Reflux;	Preparation of compound 10-1 After introducing <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (50 g, 227.3 mmol), phenyl boronic acid (30.5 g, 250 mmol), Pd(PPh3)4(13.1 g, 11.37 mmol), K2CO3(62.8 g, 454.6 mmol), toluene 600 mL, EtOH 200 mL, and purified water 200 mL in a reaction container, the mixture was stirred under reflux for 6 hours. After cooling the mixture to room temperature, an organic layer was extracted with ethylacetate (EA) and distilled water. The obtained organic layer was distilled under reduced pressure, and the residue was separated with column chromatography to obtain compound 10-1 (49 g, 99%).
99%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 6h;Reflux;	After introducing <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (50g, 227.3mmol), phenyl boronic acid (30.5g, 25Ommol), Pd(PPh3)4 (13.lg, 11.37mmol), K2C03 (62.8g, 454.6mmol), toluene (600mL), ethanol (200mL), and distilled water (200mL) into a flask, the mixture was stirred under reflux for 6 hours. After cooling to room temperature, the mixture was extracted with EA and distilled water. The obtained organic layer was distilled under reduced pressure. The residue was subjected to column chromatography to obtain compound 4-1 (49 g, yield: 99%).
99%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 6h;Reflux;	After introducing <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (50g, 227.3mmol), phenylboronic acid (30.5g, 250mmol), Pd(PPh3)4(13.1g, 11.37mmol), K2CO3(62.8g, 454.6mmol), toluene (600mL), ethanol (200mL), and H2O (200mL) into a flask, the mixture was stirred under reflux for 6 hrs, cooled to room temperature, and extracted with ethyl acetate (EA) and distilled water. The organic layer was distilled under reduced pressure. The residue was subjected to column chromatography to obtain compoundB(5-fluoro-2-nitro-1,1'-biphenyl) (49 g, yield: 99%)

99%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 6h;Reflux;	<strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (50g, 227.3mmol), phenyl step theory it buys (30.5g, 250mmol), Pd (PPh 3) 4 (13.1g, 11.37mmol), K 2 CO 3 (62.8g, 454.6mmol), 600 ml toluene, ethanol 200 ml, H 2 O 200 ml multi function cap for. 6 2000 paste has better mouth feeling and which agitates the reflux time, and cooled down to the normal temperature, ethyl acetate (EA) and a distilled extracted to. And vacuum distilling a organic layer, separated by column chromatography residue B the compounds ( 5-fluoro-2-nitro -1,1 '-biphenyl) (49 g, yield: 99%) is obtained.
94%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 120℃; for 5h;	After introducing <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (50 g, 227.3 mmol), phenylboronic acid (30.5 g, 250.0 mmol), Pd(PPh3)4 (13.1 g, 11.37 mmol), 2M K2C03 (200mL), toluene (600mL), and ethanol (200mL) into a flask, the mixture was under reflux at 120C for 5 hours. After completion of the reaction, the mixture was extracted with ethyl acetate. The remaining moisture was removed from the obtained organic layer with magnesium sulfate. The product was dried, and purified by column chromatography to obtain compound 1-1-1 (46.4 g, yield: 94%).
94%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 120℃; for 5h;	To a flask was added <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong>(50 g, 227.3 mmol),Phenylboronic acid (30.5 g, 250.0 mmol),Pd (PPh3) 4 (13.1 g, 11.37 mmol),2M K2CO3 200 mL, Dissolved in toluene (600 mL) and ethanol (200 mL), and refluxed at 120 C for 5 hours.After completion of the reaction, the organic layer was extracted with ethyl acetate, and the residue was dried over magnesium sulfate. The organic layer was dried and separated into a column to obtain Compound 1-1-1 (46.4 g, yield: 94%).
82%		At RT and under N2, Pd(PPh3)4 (114 mg, 0.098 mmol) was added to a mixture of <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (539 mg, 2.45 mmol), phenylboronic acid (364 mg, 2.94 mmol), and sodium carbonate (1.04 g, 9.80 mmol) in DMSO (degassed by freeze-pump-thaw, 25 mL). The reaction was stirred at 80 C. for 16 hours and then water (10 mL, degassed by purging) was added. The reaction was continued for 24 hours. The reaction mixture was filtered over kiezelguhr. The filtrate was diluted with aq. sat. NaHCO3 (100 mL) and extracted with EtOAc (2×50 mL). The EtOAc-extracts were washed with brine (1×50 mL). The combined EtOAc-extracts were dried (Na2SO4), filtered, and evaporated to dryness in vacuo. The crude product was purified by column chromatography (EtOAc/heptane: 1/100 to 1/20) to obtain 4-fluoro-1-nitro-2-phenylbenzene as a yellow oil (439 mg, 82%, purity (GC)>95%).MS: [M]+=217.
62%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 100℃; for 2h;	After mixing <strong>[700-36-7]2-bromo-4-fluoronitrobenzene</strong> (15 g, 68 mmol), phenyl boronic acid (9.1 g, 75 mmol), Pd(PPh3)4 (3.5 g, 2.72 mmol), Na2CO3 (18 g, 170 mmol), toluene 270 mL, ethanol 90 mL, and distilled water 90 mL, the mixture was stirred for 2 hours at 100C. After completing the reaction, the mixture was washed with distilled water, and then extracted with EA. The organic layer was dried with MgSO4, and solvent was removed with a rotary evaporator. Then, the remaining product was purified by column chromatography using MC and hexane as developing solvents to obtain compound 5-1 (9.2 g, 62 %).

Reference： [1]Patent: WO2015/178731,2015,A1 .Location in patent: Paragraph 258; 259; 260; 261
[2]Patent: WO2016/48109,2016,A1 .Location in patent: Paragraph 224; 225; 226
[3]Patent: WO2016/52962,2016,A1 .Location in patent: Paragraph 194; 195
[4]Patent: KR2016/37788,2016,A .Location in patent: Paragraph 0211-0213
[5]Patent: WO2015/167300,2015,A1 .Location in patent: Paragraph 181; 182; 183
[6]Patent: KR2016/11463,2016,A .Location in patent: Paragraph 0061-0063
[7]Patent: US2010/280268,2010,A1 .Location in patent: Page/Page column 14
[8]Patent: WO2013/109045,2013,A1 .Location in patent: Page/Page column 26-27
[9]Organic Letters,2015,vol. 17,p. 346 - 349

23
[ 700-36-7 ]
[ 109-73-9 ]
[ 951667-98-4 ]

Yield	Reaction Conditions	Operation in experiment
		At RT and under nitrogen, Pd(OAc)2 (24 mg, 0.11 mmol) and BINAP (74 mg, 0.12 mmol) were added to a solution of butylamine (173 mg, 2.37 mmol) and 4-fluoro-2-bromonitrobenzene (460 mg, 2.09 mmol) in toluene (3 mL, degassed bu purging). The reaction mixture was heated at 100 C. for 3 minutes and then cooled to 0 C. NaOtBu (271 mg, 2.82 mmol) was added and immediately the reaction mixture turned red. The reaction was stirred at 70 C. for 16 h. The reaction was cooled to RT and filtered over Kiezelguhr. The residue was rinsed with EtOAc (30 mL). The EtOAc-layer was washed with brine (30 mL). The aqueous-layer was extracted once more with EtOAc (30 mL). The combined EtOAc-extracts were dried (Na2SO4), filtered, and evaporated to drynessin vacuo. The crude product was purified by flash column chromatography (EtOAc/heptane: 1/100 to 1/30) to afford (5-fluoro-2-nitro-phenyl)-propyl-amine as a yellow oil (333 mg, 75%, purity (GC)=85%).MS: [M]+=212.

Reference： [1]Patent: US2010/280268,2010,A1 .Location in patent: Page/Page column 54-55

24
[ 700-36-7 ]
[ 109-73-9 ]
[ 951666-45-8 ]

Yield	Reaction Conditions	Operation in experiment
		Under Argon and at RT, Pd(OAc)2 (24 mg, 0.11 mmol) and BINAP (74 mg, 0.12 mmol) were added to a solution of butylamine (173 mg, 2.37 mmol) and 4-fluoro-2-bromonitrobenzene (460 mg, 2.09 mmol) in toluene (degassed by purging, 3 mL). The reaction mixture was heated at 100 C. for 3 minutes and then cooled to 0 C. Upon addition of sodium tert-butoxide (271 mg, 2.82 mmol) the reaction mixture turned red. The reaction was stirred at 70 C. for 16 hours. The reaction was cooled to RT and filtered over Kiezelguhr. The residue was rinsed with EtOAc (30 mL). The EtOAc-layer was washed with brine (30 mL). The aqueous-layer was extracted once more with EtOAc (30 mL). The combined EtOAc-extracts were dried (Na2SO4), filtered, and evaporated to dryness in vacuo. The crude product was purified by flash column chromatography (EtOAc/heptane: 1/100 to 1/30) to afford N1-butyl-5-fluoro-2-nitro-aniline as a yellow oil (333 mg, 75%, purity (GC)=85%).MS: [M]+=212.

Reference： [1]Patent: US2010/280268,2010,A1 .Location in patent: Page/Page column 18-19

25
[ 700-36-7 ]
[ 75-04-7 ]
[ 475278-46-7 ]

Yield	Reaction Conditions	Operation in experiment
71%		Under Argon and at RT, Pd(OAc)2 (33 mg, 0.15 mmol) and BINAP (101 mg, 0.16 mmol) were added to a solution of 2 M ethylamine/THF (3.8 mL, 7.6 mmol) and 4-fluoro-2-bromonitrobenzene (647 mg, 2.94 mmol) in toluene (degassed by purging, 3 mL). The reaction mixture was heated at 90 C. for 3 minutes and then cooled to 0 C. Upon addition of sodium tert-butoxide (452 mg, 4.70 mmol) the reaction mixture turned red. The reaction was stirred at 70 C. for 22 hours. The reaction was filtered over Kiezelguhr. Rinsed with EtOAc (100 mL). The filtrate was washed with brine (100 mL). The brine-layer was extracted once with EtOAc (100 mL). The combined EtOAc-extracts were dried (Na2SO4), filtered, and evaporated to dryness in vacuo. The crude product was purified by column chromatography (heptane to EtOAc/heptane: 1/20) to obtain the title compound as a yellow solid (382 mg, 71%, purity (GC)>95%).MS: [M]+=184.

Reference： [1]Patent: US2010/280268,2010,A1 .Location in patent: Page/Page column 21

26
[ 700-36-7 ]
potassium benzyltrifluoroborate [ No CAS ]
[ 777092-16-7 ]

Yield	Reaction Conditions	Operation in experiment
69%	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; water; for 46h;Inert atmosphere; Reflux;	At RT and under Argon, PdCl2(dppf) (118 mg, 0.16 mmol) was added to a suspension of <strong>[700-36-7]2-bromo-4-fluoronitrobenzene</strong> (355 mg, 1.61 mmol), potassium benzyltrifluoro-borate (353 mg, 1.78 mmol), and cesium carbonate (1.54 g, 4.73 mmol) in THF/water: 5/1 (degassed by purging, 6 mL). The reaction was warmed at reflux for 22 hours. An additional amount of potassium benzyltrifluoroborate (159 mg), PdCl2(dppf) (57 mg), THF (4 mL), and water (1 mL) were added and the reaction was continued for 24 hours. The reaction was filtered over Kiezelguhr and the residue was rinsed with THF (20 mL). THF was removed in vacuo. The residue was dissolved in EtOAc (30 mL) and was washed with brine (2×30 mL). The aqueous-layer was extracted once more with EtOAc (20 mL). The EtOAc-extracts were dried (Na2SO4), filtered, and evaporated to afford the crude product as dark brown oil. The crude product was purified by flash column chromatography (EtOAc/heptane: 1/50) to obtain the desired product as a light yellow oil (257 mg, 69%, purity (LC) n.d).NMR: 1H (CDCl3): delta 8.03 (dd, J=5.04 Hz and 8.84 Hz, 1H), 7.35-7.23 (m, 3H), 7.14-7.19 (m, 2H), 7.05 (ddd, J=2.78 Hz and 7.07 Hz and 8.84 Hz, 1H), 6.91 (dd, J=2.78 Hz and 9.09 Hz, 1H), 4.33 (s, 2H).

Reference： [1]Patent: US2010/280268,2010,A1 .Location in patent: Page/Page column 22

27
[ 700-36-7 ]
[ 103-67-3 ]
[ 951666-70-9 ]

Yield	Reaction Conditions	Operation in experiment
61%		Under Argon and at RT, Pd(OAc)2 (43 mg, 0.19 mmol) and BINAP (124 mg, 0.20 mmol) were added to a solution of benzylmethylamine (340 mg, 2.81 mmol) and 4-fluoro-2-bromonitrobenzene (624 mg, 2.81 mmol) in toluene (degassed by purging, 5 mL). The reaction mixture was heated at 100 C. for 3 minutes and then cooled to 0 C. Upon addition of sodium tert-butoxide (324 mg, 3.37 mmol) the reaction mixture turned red. The reaction was stirred at 70 C. for 20 hours. The reaction was cooled to RT and filtered over Kiezelguhr. The residue was rinsed with EtOAc (50 mL). The EtOAc-layer was washed with brine (50 mL). The EtOAc-extract was dried (Na2SO4), filtered, and evaporated to dryness in vacuo. The crude product was purified by flash column chromatography (EtOAc/heptane: 1/16) to afford Benzyl-(5-fluoro-2-nitro-phenyl)-methylamine as a yellow oil (443 mg, 61%, purity (LC) n.d.).NMR: 1H (CDCl3): delta 7.85 (dd, J=6.32 Hz and J=9.12 Hz, 1H), 7.38-7.21 (m, 5H), 6.69 (dd, J=2.52 Hz, 1H), 6.56 (ddd, J=2.52 Hz and J=7.08 Hz and J=9.08 Hz, 1H), 4.40 (s, 2H), 2.80 (s, 3H).

Reference： [1]Patent: US2010/280268,2010,A1 .Location in patent: Page/Page column 24

28
[ 700-36-7 ]
[ 108-98-5 ]
[ 242139-98-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 1h;	Example 67; Synthesis of (3S)-3-amino-1-hydroxy-6-(phenylsulfonyl)-3,4-dihydroquinolin-2(1H)-one, hydrochloride salt (72); 2-Bromo-1-nitro-4-(phenylthio)benzene (68); A mixture of <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (4.3 g, 20 mmol) and K2CO3 (5.39 g, 39.0 mmol) in DMF (100 mL) was heated to 80 C. To the mixture was added benzenethiol (2.15 g, 19.5 mmol) and the mixture was stirred at 80 C. for 1 h. The reaction mixture was quenched by the addition of water (200 mL), and extracted with EtOAc (3×400 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over Na2SO4, filtered and concentrated in vacuo to afford the product as a yellow solid (6 g, 99%), which was used for the next step without further purification.

Reference： [1]Patent: US2010/324043,2010,A1 .Location in patent: Page/Page column 38

29
[ 700-36-7 ]
[ 108-95-2 ]
[ 1258545-24-2 ]

Yield	Reaction Conditions	Operation in experiment
94%		Example 71; Synthesis of (3S)-3-amino-1-hydroxy-6-phenoxy-3,4-dihydroquinolin-2(1H)-one, hydrochloride salt (93); 2-Bromo-1-nitro-4-phenoxybenzene (90); Phenol (11.1 g, 118 mmol) was added to a suspension of Cs2CO3 (46.2 g, 142 mmol) in MeCN (295 mL). The resulting solution was stirred at RT for 10 min, then <strong>[700-36-7]2-bromo-4-fluoronitrobenzene</strong> (26.0 g, 118 mmol) was added, and the reaction mixture was heated to 50 C. for 65 h. The reaction mixture was cooled to RT and filtered to remove Cs2CO3. The filtrate was concentrated in vacuo, and the resulting residue was dissolved in EtOAc (150 mL) and washed with aqueous sodium hydroxide solution (1 N, 250 mL), water (2×250 mL), and saturated aqueous sodium chloride solution (250 mL). The separated organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. Purification by silica gel chromatography (Eluant: heptane) provided the title compound as a pale yellow oil (32.7 g, 94%). 1H NMR (400 MHz, CDCl3) delta 6.97 (dd, J=9.1, 2.6 Hz, 1H), 7.08-7.12 (m, 2H), 7.26-7.31 (m, 2H), 7.43-7.49 (m, 2H), 7.95 (d, J=9.1 Hz, 1H).

Reference： [1]Patent: US2010/324043,2010,A1 .Location in patent: Page/Page column 44
[2]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 37 - 40

30
[ 700-36-7 ]
[ 93267-04-0 ]
methyl N-(tert-butoxycarbonyl)-3-fluoro-6-nitro-L-phenylalaninate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%		General procedure: A 1 M stock of the zincate was prepared as follows: To a suspension of zinc powder (196 mg, 2.0 equiv, based on the iodoserine, dried under vacuum using a heat gun) was added DMF (0.7 mL) and catalytic iodine (50 mg, 0.19 mmol). The reaction mixture turned from colorless to red to colorless again in ?2 min. After the return to colorless a DMF solution (1.9 mL) of the iodoserine was added followed by additional iodine (50 mg). The reaction turned from pale yellow to red, and back to colorless with an associated exotherm. The solution was stirred until the exotherm subsided, was cooled to room temp (?25 min) and was stirred until the iodoserine disappeared as monitored by TLC. The zincate solution was syringed away from the excess zinc and was added to a separate flask containing Pd(OAc)2 (4 mg, 0.018 mmol), X-Phos (15 mg, 0.032 mmol), and the aryl bromide (1.88 mmol) in DMF (0.5 mL). The resulting mixture was stirred at room temperature overnight. Upon completion as indicated by TLC, the reaction was quenched with satd NH4Cl (10 mL), poured into H2O (50 mL) and extracted with EtOAc (2 × 50 mL). The organic layers were washed with H2O (2 × 100 mL), brine (1 × 100 mL), dried over MgSO4, filtered, and concentrated to a crude oil. The desired material was isolated via flash chromatography.

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 5211 - 5213

31
[ 150-19-6 ]
[ 700-36-7 ]
[ 1428308-04-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	With caesium carbonate; In acetonitrile; at 0 - 20℃; for 12h;	Step 1. Synthesis of 2-bromo-4-(3-methoxyphenoxy)-1 -nitrobenzene (C1). To a 0 C solution of 2-bromo-4-fluoro-1 -nitrobenzene (20 g, 91 mmol) in acetonitrile (300 mL) was added cesium carbonate (36 g, 110 mmol) followed by 3-methoxyphenol (12.0 ml, 109 mmol), and the reaction mixture was stirred for 12 hours at room temperature. Solvent was removed in vacuo, and the residue was diluted with ethyl acetate and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography (Eluent: 1 % ethyl acetate in petroleum ether) afforded the product as a pale yellow liquid. Yield: 24.8 g, 76.5 mmol, 84%. GCMS m/z 323.1 [M+]. 1 H NMR (400 MHz, DMSO-ci6) delta 8.1 0 (d, J=9.1 Hz, 1 H), 7.44 (d, J=2.6 Hz, 1 H), 7.40 (dd, J=8.4, 8.1 Hz, 1 H), 7.1 1 (dd, J=9.1 , 2.6 Hz, 1 H), 6.89 (br dd, J=8.4, 2.3 Hz, 1 H), 6.80 (br dd, J=2.6, 2.3 Hz, 1 H), 6.75 (br dd, J=7.9, 2.3 Hz, 1 H), 3.77 (s, 3H).

Reference： [1]MedChemComm,2013,vol. 4,p. 125 - 129
[2]Patent: WO2013/186666,2013,A1 .Location in patent: Page/Page column 25; 26

32
[ 67-56-1 ]
[ 700-36-7 ]
[ 98447-30-4 ]

Yield	Reaction Conditions	Operation in experiment
68%	With tetrabutylammomium bromide; sodium hydroxide; In dichloromethane; water; at 25 - 40℃; for 16h;	To a solution of 2-bromo-4-fluoro-1-nitro-benzene (60.0 g, 273 mmol, 1.00 eq) in the mixture of dichloromethane (400 mL) and methanol (440 mL) was added 1 M NaOH aqueous solution (1.00 L). Then a catalytic amount of TBAB (tetrabutylammonium bromide, 360 mg, 1.26 mmol) was added. The reaction was stirred at 40C for 16 h. The reaction mixture was partitioned between DCM and water. Then the aqueous layer was extracted with dichloromethane (3 x 300 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel to give Compound 29 (43.1 g, 186 mmol, 68% yield) as a yellow solid.?H NMR: (400 MHz, Chloroform-d) 8.00 (d, J= 9.3 Hz, 1H), 7.23 (d, J 2.6 Hz, 1H), 6.93 (dd, J= 2.6, 9.3 Hz, 1H), 3.90 (s, 3H).
	With tetrabutylammomium bromide; sodium hydroxide; In dichloromethane; at 20℃; for 16h;	2-Bromo-4-fluoro-l- nitro-benzene (500 mg, 2.28 mmol, 1.0 equiv) was dissolved in a 1 : 1 mixture of DCM and NaOH aqueous solution (IN) (10 mL), alcohol (MeOH or EtOH) was added in large excess (2 mL). A catalytic amount of TBAB (3 mg) was added and the reaction was stirred at room temperature for 16h. LCMS showed completion of the reaction. The mixture was partitioned between water and DCM. The aqueous layer was extracted with DCM (3x 50 mL). The combined organic layer was washed with 0.1M HC1 solution (4x 30 mL), dried over Na2S04, filtered and concentrated in vacuo to afford the desired material.
43.1 g	With tetrabutylammomium bromide; sodium hydroxide; In dichloromethane; water; at 25 - 40℃; for 16h;	2-bromo-4-fluoro-1-nitrobenzene(60.0g, 273mmol, 1.00 equivalents)Add in a solution of a mixture of dichloromethane (400 mL) and methanol (440 mL)1M aqueous NaOH solution (1.00 L). Then add a catalytic amount of TBAB(tetrabutylammonium bromide, 360 mg, 1.26 mmol).The reaction was stirred at 40 C for 16 hours.The reaction mixture was partitioned between DCM and water. The aqueous layer was then extracted with dichloromethane (3×300 mL).The combined organic layers were dried over Na 2 SO 4 ,Filter and concentrate under reduced pressure. The crude product was purified by silica gel column chromatography to give a solid compoundI-29 (43.1 g, 186 mmol).

Reference： [1]Patent: WO2017/160569,2017,A1 .Location in patent: Paragraph 00285; 00286
[2]Patent: WO2013/117645,2013,A1 .Location in patent: Paragraph 00513
[3]Patent: CN108779119,2018,A .Location in patent: Paragraph 0413; 0415; 0416; 0417; 0825; 0827-0829; 0869

33
[ 700-36-7 ]
[ 1993-03-9 ]
2',5-difluoro-2-nitro-1,1'-biphenyl [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl acetamide; water; at 110℃;Inert atmosphere;	Preparation 53 2',5-Difluoro-2-nitro-1,1'-biphenyl To a solution of <strong>[700-36-7]2-bromo-4-fluoronitrobenzene</strong> (1.500 g, 6.8 mmol), 2-fluorophenylboronic acid (1.145 g, 8.2 mmol), N,N-dimethylacetamide (50 mL), and 2.0 M aqueous potassium carbonate (10 mL) under argon was added tetrakis(triphenylphosphine)palladium (0) (0.394 g, 0.3 mmol). The mixture was stirred at 110 C. for 6 hrs. After cooling to room temperature, the mixture was partitioned between ethyl acetate (100 mL) and water. The organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous sodium sulfate), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (0-30% methylene chloride/hexanes) to afford a light yellow oil (1.5 g, 94%). 1H NMR (300 MHz, CDCl3) delta 8.12 (dd, 1H, J=9.0, 5.1 Hz), 7.44 (m, 1H), 7.34 (td, 1H, J=7.5, 2.1 Hz), 7.31-7.10 (m, 4H).

Reference： [1]Patent: US2013/303524,2013,A1 .Location in patent: Paragraph 0343-0344

34
[ 700-36-7 ]
[ 13154-14-8 ]
[ 883001-24-9 ]

Yield	Reaction Conditions	Operation in experiment
39%	In tetrahydrofuran; at -60℃; for 1h;Inert atmosphere;	(46b). To a solution of <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (45b)(13.7 g, 62.5 mmol) in THF (20 mL) at -60 C was added 1-propenylmagnesium bromide (500 mL, 0.5M in THF, 250 mmol)dropwise. The reaction mixture was stirred at -60 C for 1 h,quenched with saturated aqueous NH4Cl (100 mL) and extractedwith EtOAc (2 500 mL). The combined organic layers were driedover Na2SO4 and concentrated under vacuum. The crude residuewas purified by silica gel column chromatography, eluting with50:1 petroleum ether: EtOAc, to give 46b (5.6 g, 39%) as a lightbrown oil. 1H NMR (300 MHz, CDCl3) d 8.02 (s, 1H), 7.17-7.12 (m,2H), 7.06 (s, 1H), 2.27 (d, 3H, J = 1.6 Hz). GC-MS 227 [M]+.

Reference： [1]Organic Process Research and Development,2007,vol. 11,p. 747 - 753
[2]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3947 - 3963

35
[ 143-16-8 ]
[ 700-36-7 ]
[ 1542259-25-5 ]

Yield	Reaction Conditions	Operation in experiment
40%	With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 48h;	To a solution of <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (13.30 g, 60.5 mmol) in DMF (100 mL) were added K2C03 (16.78 g, 121 mmol) and dihexylamine (11.22 g, 60.5 mmol), and the mixture was stirred at 90 C for 48 h. The mixture was cooled to rt and filtered and the filtrate was concentrated to 30 mL. The resulting solution was poured into 150 mL of DCM and washed with water (150 mL x 3), brine (150 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE / EtOAc (V / V) = 10: 1) to give the title compound as yellow oil (9.28 g, 40%).

Reference： [1]Patent: WO2014/12360,2014,A1 .Location in patent: Paragraph 00425

36
[ 29526-99-6 ]
[ 700-36-7 ]
2-bromo-4-(1-methylcyclopropoxy)-1-nitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0 - 20℃;	To a cold (0 C), stirred mixture of <strong>[700-36-7]2-bromo-4-fluoronitrobenzene</strong> (10.0 g, 45.5 mmol) and 1-methylcyclopropanol (3.61 g, 50.0 mmol) in DMF (200 ml) was added NaH (2.36 g of 60% in oil, 59.1 mmol) in portions. Once the addition was complete the cold bath was removed and the mixture was stirred at rt for 5 h. The reaction was quenched with water and extracted with EtOAc (x3). The combined organic layers were washed with water (x3), brine (x2), dried, filtered and concentrated to leave an oil which was purified by column chromatography (elution with 100:0 to 20:1 hexane:EtOAc) to yield the desired product as a light yellow oil.
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0 - 20℃; for 5h;	To a cold (0 C), stirred mixture of <strong>[700-36-7]2-bromo-4-fluoronitrobenzene</strong> (10.0 g, 45.5 mmol) and 1 -methylcyclopropanol (3.61 g, 50.0 mmol) in DMF (200 ml) was added NaH (2.36 g of 60% in oil, 59.1 mmol) in portions. Once the addition was complete, the cold bath was removed and the mixture was stirred at room temperature for 5 h. The reaction was quenched with water and extracted with EtOAc (x3). The combined organic layers were washed with water (x3), brine (x2), dried, filtered and concentrated to leave an oil which was purified by column chromatography (Si02: gradient elution with 100:0 to 20:1 hexane:EtOAc) to yield the desired product.
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0 - 20℃; for 5h;	To a cold (0 C), stirred mixture of <strong>[700-36-7]2-bromo-4-fluoronitrobenzene</strong> (10.0 g, 45.5 mmol) and 1-methylcyclopropanol (3.61 g, 50.0 mmol) in DMF (200 ml) was added NaH (2.36 g of 60% in oil, 59.1 mmol) in portions. Once the addition was complete, the cold bath was removed and the mixture was stirred at room temperature for 5 h. The reaction was quenched with water and extracted with EtOAc (x3). The combined organic layers were washed with water (x3), brine (x2), dried, filtered and concentrated to leave an oil which was purified by column chromatography (Si02: gradient elution with 100:0 to 20:1 hexane:EtOAc) to yield the desired product.

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 2983 - 2992
[2]Patent: WO2014/134776,2014,A1 .Location in patent: Page/Page column 44
[3]Patent: WO2014/137723,2014,A1 .Location in patent: Page/Page column 34
[4]Patent: WO2014/134774,2014,A1 .Location in patent: Page/Page column 33
[5]Patent: WO2020/81682,2020,A1 .Location in patent: Paragraph 0192

37
[ 700-36-7 ]
3-ethyloxetan-3-ol [ No CAS ]
C₁₁H₁₂BrNO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0 - 20℃; for 5h;	To a cold (0 C), stirred solution of 2-bromo-4-fluoro-l -nitrobenzene (8.8 g, 40 mmol) and 3-ethyloxetan-3-ol (4.5 g, 44 mmol) in DMF (100 mL) was added NaH (60%, 2.2 g, 44 mmol) in portions. The reaction mixture was then stirred at room temperature for 5 h, quenched with cold water (500 mL) and, extracted with EtOAc (2 x 150 mL). The combined organic layers were washed with water (200 mL), brine (200 mL), dried over Na2S04, filtered and concentrated under reduced pressure to yield a residue which was purified by column chromatography on silica gel (gradient elution with petroleum ether:EtOAc 50: 1 to 5:1) to afford the aryl ether. MS (ESI) m/z = 304.0 [M+H]+.

Reference： [1]Patent: WO2014/137723,2014,A1 .Location in patent: Page/Page column 81
[2]Patent: WO2014/134774,2014,A1 .Location in patent: Page/Page column 80

38
[ 700-36-7 ]
[ 122-39-4 ]
C₁₈H₁₃BrN₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃; for 2h;Inert atmosphere;	4. The reaction was performed under nitrogen. Diphenylamine (0.77 g, 4.55 mmol) and potassium tert-butoxide (0.51 g, 4.55 mmol) were stirred in DMSO (2.5 mL; 99.7%, degassed, extra dry, over mol. sieve, water <50 ppm, Acros) at room temperature until all solids had dissolved to give a green solution of the diphenylamide anion. It was slowly added to a solution of <strong>[700-36-7]2-bromo-4-fluoronitrobenzene</strong> (1 g, 4.55 mmol) in DMSO (2.5 mL; 99.7%, degassed, extra dry, over mol. sieve, water <50 ppm, Acros), which was kept in a water bath at room temperature to dissipate the evolving heat. The reaction was strongly exothermic. The color of the mixture became dark red. The sequence and the slow rate of addition are required to minimize the formation of by-products resulting from substitution of bromine, instead of fluorine, and from bis-substitution. After the heat evolution finished, the mixture was stirred at room temperature for 2 h. It was extracted with water and CH2Cl2. The red organic layer was evaporated. It contained at least two main products, which could not be separated by chromatography. Chromatography (20 g of silica; 1/1 of hexane/CH2Cl2) was performed to remove the polar impurities. The crude target fraction was evaporated to dryness. The residue was dissolved in CH2Cl2. Heptane (25 mL) was added. CH2Cl2 was rotor-evaporated to give a suspension of the product in heptane. It was allowed to settle at room temperature for less than 1 h. It was filtered to give a yellow solid product and a dark red filtrate. The solid was washed with ice-cold hexane. Yellow solid: 745 mg (2.02 mmol, 44%; C18H13BrN2O2; MW 369.21).

Reference： [1]Inorganica Chimica Acta,2015,vol. 427,p. 81 - 86

39
[ 700-36-7 ]
[ 1537905-39-7 ]
5-[9-(3-bromo-4-nitrophenyl)carbazole-3-yl]benzimidazolo[1,2-a]benzimidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate; In dimethyl sulfoxide; at 100℃; for 16h;Inert atmosphere;	931 mg (2.50 mmol) 5-(9H-carbazol-3-yl)benzimidazolo[1,2-a]benzimidazole, 578 mg (2.60 mmol) <strong>[700-36-7]2-bromo-4-fluoro-1-nitro-benzene</strong> and 435 mg (3.20 mmol) potassium carbonate in 10 ml DMSO are stirred under nitrogen at 100 C. After 16 h the reaction mixture is poured into water and the product is filtered off. The product is washed with water and ethanol (yield: 1.21 g (85 %)). 1 H NMR (400 MHz, CDCl3): delta 8.45-8.46 (m, 1 H), 8.21-8.24 (m, 2H), 8.1 1 (d, J 7.88-7.96 (m. 4H), 7.71-7.74 (m, 1 H), 7.53-7.60 (m, 3H), 7.38-7.50 (m, 6H). MS (APCI(pos), mlz): 572, 574(M+1).

Reference： [1]Patent: WO2015/14791,2015,A1 .Location in patent: Page/Page column 118; 119

40
[ 700-36-7 ]
[ 28890-99-5 ]
C₁₉H₁₁BrN₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In dimethyl sulfoxide; at 100℃; for 1h;Inert atmosphere;	A mixture of 4.80 g (23.0 mmol) 6H-benzimidazolo[1 ,2-a]benzimidazole, 5.10 g (23.0 mmol) 2-bromo-4-fluoro-2-nitrobenzene and 3.68 g (27.0 mmol) potassium carbonate in 63 ml dimethylsulfoxide (DMSO) is stirred under argon at 100 C for 1 h, cooled to 20 C and poured into 240 ml water. The product is filtered off and is washed with water. Yield 8.84 g (100 %). 1H NMR (400 MHz, CDCl3): delta 8.42 (s, 1 H), 8.20 (s, 2H), 7.82-7.89 (m, 3H), 7.70-7.72 (m, 1H), 7.36-7.52 (m, 4H)

Reference： [1]Patent: WO2015/14791,2015,A1 .Location in patent: Page/Page column 116

41
[ 700-36-7 ]
[ 28890-99-5 ]
C₂₆H₁₅N₅S [ No CAS ]

Reference： [1]Patent: WO2015/14791,2015,A1

42
[ 6418-38-8 ]
[ 700-36-7 ]
2-bromo-4-(2,3-difluoro-phenoxy)-1-nitro-benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 3h;	A mixture of <strong>[700-36-7]2-bromo-4-fluoro-1-nitro-benzene</strong> (4.42 g, 20 mmol), 2,3-difluorophenol (1.91 g,14.7 mmol) and Cs2CO3 (7.18 g, 22 mmol) in DMF (30 mL) was heated at 120 C for 3 h. EtOAc was added and the mixture was washed with water and brine. The organic layer was dried, filtered, and evaporated. The residue was purified by chromatography (silica gel, 0-10% EtOAc/hexanes) to give 2-bromo-4-(2,3-difluoro-phenoxy)-1-nitro-benzene (4.1 g, 70%) as alight yellow solid.

Reference： [1]Patent: WO2015/86642,2015,A1 .Location in patent: Page/Page column 108

43
[ 110-91-8 ]
[ 700-36-7 ]
4-(5'-fluoro-2'-nitrophenyl)morpholine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 110℃; for 8h;	Commercially available <strong>[700-36-7]2-bromo-4-fluoro-nitrobenzene</strong> (1 .5 g, 6.82 mmol) was combined with palladium(ll) acetate (0.16 g, 0.8 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.62 g, 0.8 mmol) and cesium carbonate (4.44 g, 13.64 mmol). To the mixture was then added degassed 1 ,4-dioxane (15 mL) and morpholine (0.84 g, 9.6 mmol). The reaction mixture was heated at ~110C in a sand-bath for 8 h. The reaction mixture was cooled to room temperatureand diluted with ethyl acetate (150 mL), water, (20 mL) and brine (20 mL). The organic phase was separated, dried over Na2S04, filtered and the solvents were removed under reduced pressure. The residue was purified on HP-Sil SNAP cartridges using a Biotage Isolera One purification system employing an EtOAc/n-heptane gradient (5/95 -> 40/60) to afford the title compound as a yellow oil (0.59 g, 38 %). 1H-NMR (400 MHz, CDCI3): delta = 3.05-3.09 (m, 4H), 3.84-3.88 (m, 4H), 6.72-6.77 (m, 1 H), 6.78 (dd, 1 H), 7.91 (dd, 1 H)
38%	With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 110℃; for 8h;	(0692) Step A (0693) Commercially available <strong>[700-36-7]2-bromo-4-fluoro-nitrobenzene</strong> (1.5 g, 6.82 mmol) was combined with palladium(II) acetate (0.16 g, 0.8 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.62 g, 0.8 mmol) and cesium carbonate (4.44 g, 13.64 mmol). To the mixture was then added degassed 1,4-dioxane (15 mL) and morpholine (0.84 g, 9.6 mmol). The reaction mixture was heated at 110 C. in a sand-bath for 8 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (150 mL), water, (20 mL) and brine (20 mL). The organic phase was separated, dried over Na2SO4, filtered and the solvents were removed under reduced pressure. The residue was purified on HP-Sil SNAP cartridges using a Biotage Isolera One purification system employing an EtOAc/n-heptane gradient (5/95->40/60) to afford the title compound as a yellow oil (0.59 g, 38%). (0694) 1H-NMR (400 MHz, CDCl3): delta=3.05-3.09 (m, 4H), 3.84-3.88 (m, 4H), 6.72-6.77 (m, 1H), 6.78 (dd, 1H), 7.91 (dd, 1H).

Reference： [1]Patent: WO2015/110263,2015,A1 .Location in patent: Page/Page column 147
[2]Patent: US2017/2005,2017,A1 .Location in patent: Paragraph 0691; 0692; 0693; 0694

44
[ 110-89-4 ]
[ 700-36-7 ]
1-(3-bromo-4-nitrophenyl)piperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With potassium carbonate; In N,N-dimethyl-formamide; at 75℃;	Into a 1000-mL round-bottom flask, was placed a solution of <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (30 g, 137.61 mmol, 1.00 equiv) in N,N-dimethylformamide (450 mL), piperidine (13.974 g, 162.68 mmol, 1.20 equiv), and potassium carbonate (56.718 g, 411.00 mmol, 2.99 equiv). The resulting solution was stirred overnight at 75 C. in an oil bath. The solids were filtered out. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 300 mL of dichloromethane. The resulting mixture was washed with 2100 mL of water and 2100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:50). This resulted in 19 g (49%) of 1-(3-bromo-4-nitrophenyl)piperidine as a yellow solid.

Reference： [1]Patent: US9301951,2016,B2 .Location in patent: Page/Page column 33

45
[ 700-36-7 ]
[ 653-92-9 ]
methyl 5,5'-difluoro-2'-nitrobiphenyl-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
279.8 mg	With tris-(dibenzylideneacetone)dipalladium(0); copper; In dimethyl sulfoxide; at 100℃; for 2h;	Example 38a Methyl 5,5'-difluoro-2'-nitrobiphenyl-2-carboxylate To <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (185.16 mg, 0.842 mmol) was added Pd2dba3 (23.12 mg, 0.025 mmol) and copper powder (271 mg, 4.26 mmol). Dimethylsulfoxide (2.3 ml) and methyl 2-bromo-4-fluorobenzoate (0.122 ml, 0.842 mmol) were added and the mixture was stirred vigorously at 100 C. for 2 h. The mixture was cooled to room temperature, diluted with ethyl acetate (20 ml), and filtered. The filtrate was washed with water and dried (anhydrous Na2SO4) and concentrated to give a yellow oil (279.8 mg). This oil was utilized without purification for the preparation of Example 38b.
279.8 mg	With tris-(dibenzylideneacetone)dipalladium(0); copper; In dimethyl sulfoxide; at 100℃; for 2h;	<strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong>(185.16mg, 0.842mmol) to was added Pd 2 dba 3 (23.12mg, 0.025mmol) and copperpowder a (271mg, 4.26mmol). Dimethyl sulfoxide (2.3 ml) and methyl2-bromo-4-fluorobenzoate (0.122ml, 0.842mmol) was added and the mixture wasstirred vigorously for 2 hours at 100 C. The mixture was cooled to roomtemperature, diluted with ethyl acetate (20 ml), and filtered. The filtrate waswashed with water, dried (anhydrous Na 2 SO 4), and concentrated to give ayellow oil (279.8mg). It was used in the preparation of Example 38b withoutpurification this oil.

Reference： [1]Patent: US9309279,2016,B2 .Location in patent: Page/Page column 61; 62
[2]Patent: JP5902123,2016,B2 .Location in patent: Paragraph 0294

46
[ 700-36-7 ]
[ 13922-41-3 ]
C₁₆H₁₀FNO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 4h;	After introducing <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (30g, 136.36 mmol), 1-naphthyl boronic acid (28g, 163,64 mmol), tetrakis(triphenylphosphine)palladium (4.7g, 4.09 mmol), potassium carbonate (47 g, 340.90 mmol), toluene (690mL), and ethanol (170mL) into a reaction vessel, distilled water (170mL) was added thereto. The mixture was stirred at 120C for 4 hours. After completion of the reaction, the mixture was washed with distilled water, and extracted with ethyl acetate. The obtained organic layer was dried with magnesium sulfate, dried by rotary evaporator to remove a solvent, and subjected to column chromatography to obtain compound 8-1 (33g, yield:92%).

Reference： [1]Patent: WO2016/48109,2016,A1 .Location in patent: Paragraph 263; 264; 265; 274; 275; 276

47
[ 320-98-9 ]
[ 700-36-7 ]

Yield	Reaction Conditions	Operation in experiment
33%	With 2.9-dimethyl-1,10-phenanthroline; oxygen; copper (I) acetate; silver sulfate; sodium bromide; In dimethyl sulfoxide; at 160℃; for 24h;Schlenk technique;	Silak reaction tube equipped with a magnetic stirrer was charged with 6.2 mg of silver sulfate,36.3 mg of copper acetate, 12.5 mg of 2,9-dimethyl-1,10-o-phenanthroline,37 mg of 2-nitro-5-fluorobenzoic acid and 30.9 mg of sodium bromide4 mL of dimethyl sulfoxide. Heat 160 C in the presence of oxygenReaction for 24 hours. After the reaction was completed, distilled water was added to quench the reaction,Extraction with ethyl acetate 3 times, each time 10mL,The combined organic phases were concentrated to give 14.5 mg of 2-nitro-5-fluorobromobenzene,The yield is 33%.

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 2794 - 2803
[2]Patent: CN107325002,2017,A .Location in patent: Paragraph 0079

48
[ 700-36-7 ]
[ 374538-03-1 ]
methyl 5'-fluoro-2'-nitro-biphenyl-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56.6%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; sodium carbonate; In ethanol; at 100℃; for 0.5h;Microwave irradiation;	Example 37a 5'-Fluoro-2'-nitrobiphenyl-2-carboxylate To a microwave vessel was added 2-(methoxycarbonyl)phenylboronic acid (63.4 mg, 0.352 mmol), <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (77 mg, 0.35 mmol), diacetoxypalladium (0.93 mg, 4.1 mumol) and dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (3.47 mg, 8.45 mumol). Ethanol (1760 mul) and sodium carbonate (176 mul, 0.352 mmol) were added and the mixture was reacted in a microwave reactor at 100 C. for 30 min. The reaction mixture was diluted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography (eluant: 9:1 hexane/ethyl acetate) to provide methyl 5'-fluoro-2'-nitrobiphenyl-2-carboxylate (37a, 54.8 mg, 0.199 mmol, 56.6% yield).
56.6%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; sodium hydrogencarbonate; In ethanol; at 100℃; for 0.5h;Microwave irradiation;	Example 37a5'-fluoro-2'-nitro-biphenyl-2-carboxylate In a microwave container, 2- (methoxycarbonyl) phenyl boronic acid(63.4mg, 0.352mmol), 2- bromo-4-fluoro-1-nitrobenzene (77mg, 0.35mmol),diacetoxy palladium (0.93mg , 4.1mumol) and dicyclohexyl (2 ',6'-dimethoxy-biphenyl-2-yl)phosphine (3.47mg, 8.45mumol). Ethanol (1760mul) and sodium carbonate (176mul,0.352mmol) was added and the mixture was allowed to react for 30 minutes in amicrowave reactor 100 C. The reaction mixture was diluted withdichloromethane, dried over anhydrous sodium sulfate, filtered, andconcentrated in vacuo. Preparative thin layer chromatography The residue waspurified by (eluent: 9: 1 hexane / ethyl acetate) to give methyl5'-fluoro-2'-nitro-biphenyl-2-carboxylate (37a, 54.8 mg , 0.199mmol, 56.6%yield).

Reference： [1]Patent: US9309279,2016,B2 .Location in patent: Page/Page column 60
[2]Patent: JP5902123,2016,B2 .Location in patent: Paragraph 0284-0285

49
[ 123-42-2 ]
[ 700-36-7 ]
[ 1266659-06-6 ]

Yield	Reaction Conditions	Operation in experiment
	With palladium diacetate; caesium carbonate; triphenylphosphine; In toluene; at 120℃; for 7h;Inert atmosphere;	palladium acetate (0.025mmol, 6 mg), triphenylphosphine (0.10mmol, 26 mg), cesium carbonate (0.75mmol, 244 mg) and 1g (0.5mmol, 110 mg) is put into the 25 ml reaction tube, sufficient vacuum, nitrogen (three times). Under the protection of nitrogen injected into the injector 2a diacetonealcohol (3.0mmol, 348 mg), toluene 3 ml. In the 120 C pot oil bath stirring 7h, after cooling to room temperature the temperature of the reaction system by adding 20 ml water, add 25 ml ethyl acetate extraction, grass-roots takes has saturated salt water for washing, for Na2 SO4 Drying, then adding a small amount of silica gel turns on lathe the main column chromatography.

Reference： [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 10511 - 10515
[2]Patent: CN106631968,2017,A .Location in patent: Paragraph 0069-0073

50
[ 584-13-4 ]
[ 700-36-7 ]
N-(3-bromo-4-nitrophenyl)-4H-1,2,4-triazol-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61.13%		When 4-amino-4H-1,2,4-triazole (1.644 g, 19.57 mmol) was solvated in 20 ml DMSO, KOtBu (2.192 g, 19.57 mmol) was added and the mixture was stirred for 0.5 h at room temperature. Subsequently,<strong>[700-36-7]2-bromo-4-fluorobenzonitrile</strong> (2.152 g, 9.785 mmol) was added and stirring was continued for one more hour and then the mixture was poured into crushed ice and neutralized with 2 M KHSO4. The white precipitate was filtered and washed with distilled water and then it was dried at 60C over night. Finally it was purified by silica gel column chromatography (PE/EA) and recrystallized using (Hexane/EA) to give compound 1 (1.698 g,61.13%) as light yellow crystals. dH (400 MHz, DMSO-d6) 10.52 (s, 1H), 8.89 (s, 2H), 8.05 (d,J = 8.8 Hz, 1H), 6.81 (s, 1H), 6.58 (d, J = 8.8 Hz, 1H).dC (100 MHz, DMSO-d6) 151.88, 144.38, 141.70, 129.20, 117.19,116.70, 111.72.

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 4723 - 4730

51
[ 1218791-12-8 ]
[ 700-36-7 ]
4-(2-amino-5-bromopyridin-3-yl)-2-chlorobenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate In N,N-dimethyl-formamide Inert atmosphere;	29.2 Step 2. 4-(2-amino-5-bromopyridin-3-yl)-2-chlorobenzamide (2-69) A mixture of 2-68 (1.01 g, 3.6 mmol), 2-3 (897 mg, 3 mmol), Pd(PPh3)2C12 (210 mg, 0.3 mmol), K3P04 (1.27 g, 6 mmol) and DMF (15 mL) was degassed with N2 and stirred at 45 °C overnight. The resulting mixture was filtered and the filtrate was concentrated and purified via column chromatography on silica gel eluting with PE/ethyl acetate from 2/1 to 1/2 to provide intermediate 2-69 (yellow solid, 381 mg, 39% yield). LCMS (m/z): 326 [M+Hj .

Reference： [1]Current Patent Assignee: DANA-FARBER CANCER INSTITUTE - WO2016/161145, 2016, A1 Location in patent: Paragraph 00741

52
[ 1396776-45-6 ]
[ 700-36-7 ]
6-(2-amino-5-(5-fluoro-2-nitrophenyl)pyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; bis(pinacol)diborane; In 1,4-dioxane; at 110℃;Inert atmosphere;	To a mixture of <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (2-8, 116.0 mg, 0.71 mmol), 6- (2-amino-5-bromopyridin-3 -yl)-3,4-dihydroisoquinolin- 1 (2H)-one (2-4, 150.0 mg, 0.47 mmol), bis(pinacolato)diborane (238.8 mg, 0.94 mmol) and KOAc (138.2 mg, 1.41 mmol) in dioxane (3 mL) under an atmosphere of argon was added Pd(dppf)C12 (38.3 mg, 0.05 mol). The resulting reaction mixture was stirred at 110 C overnight and then cooled, filtered and concentrated in vacuo. The resulting residue was purified by prep-HPLC (C18 column, CH3CN/H20, containing 0.05%NH4HCO3) to provide compound 1-7 (yellow solid, 17 mg, 10% yield). ?H NMR (400 MHz, MeOD) oe: 8.09 (dd, J, = 8.8 Hz, J2 = 5.2 Hz, 1 H), 7.91-7.98 (m, 3H), 7.57 (dd, J,= 9.6 Hz, J2= 3.2 Hz, 1 H), 7.41-7.46 (m, 4 H), 6.15 (s, 2 H), 3.41 (t, J 6.4 Hz, 2 H), 2.96 (t, J 6.4 Hz, 2 H). LCMS (m/z): 379 [M + HI .

Reference： [1]Patent: WO2016/161145,2016,A1 .Location in patent: Paragraph 00683

53
[ 700-36-7 ]
[ 1627091-47-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 5 h / 0 - 20 °C 2.1: potassium carbonate; caesium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 3.1: ammonium formate; palladium 10% on activated carbon / ethanol / 5 h / 20 °C 4.1: triethylamine / dichloromethane / 16 h / 0 - 20 °C 5.1: acetic anhydride; isopentyl nitrite; potassium acetate / toluene / 16 h / 80 °C 6.1: ammonia / methanol / 2 h / 20 °C 7.1: N-Methyldicyclohexylamine / tetrahydrofuran / 16 h / 20 °C 8.1: n-butyllithium / tetrahydrofuran / 0.33 h / -78 - -20 °C 8.2: 5 h / -78 - 20 °C 9.1: triethylamine / dimethyl sulfoxide / 2 h / 100 °C / Sealed tube 10.1: hydrogenchloride / methanol; 1,4-dioxane / 0.5 h / 65 °C

Reference： [1]Scott, Jack D.; DeMong, Duane E.; Greshock, Thomas J.; Basu, Kallol; Dai, Xing; Harris, Joel; Hruza, Alan; Li, Sarah W.; Lin, Sue-Ing; Liu, Hong; Macala, Megan K.; Hu, Zhiyong; Mei, Hong; Zhang, Honglu; Walsh, Paul; Poirier, Marc; Shi, Zhi-Cai; Xiao, Li; Agnihotri, Gautam; Baptista, Marco A. S.; Columbus, John; Fell, Matthew J.; Hyde, Lynn A.; Kuvelkar, Reshma; Lin, Yinghui; Mirescu, Christian; Morrow, John A.; Yin, Zhizhang; Zhang, Xiaoping; Zhou, Xiaoping; Chang, Ronald K.; Embrey, Mark W.; Sanders, John M.; Tiscia, Heather E.; Drolet, Robert E.; Kern, Jonathan T.; Sur, Sylvie M.; Renger, John J.; Bilodeau, Mark T.; Kennedy, Matthew E.; Parker, Eric M.; Stamford, Andrew W.; Nargund, Ravi; McCauley, John A.; Miller, Michael W. [Journal of Medicinal Chemistry, 2017, vol. 60, # 7, p. 2983 - 2992]

54
[ 700-36-7 ]
[ 124-41-4 ]
[ 98447-30-4 ]

Yield	Reaction Conditions	Operation in experiment
81%	In tetrahydrofuran; at 20℃;	To a solution of 2-bromo-4-fluoro-1-nitrobenzene (2 g, 9.09 mmol) in THF (30 mL) was added sodium methoxide (1.48 g, 27 mmol). The mixture was stirred at roomtemperature overnight. Solvent was removed under vacuum and the residual was diluted with EtOAc, quenched with saturated ammonium chloride. The organic layer was washed with saturated sodium bicarbonate, brine, dried over sodium sulfate and concentrated. The crude product was purified with flash chromatography (loading in chloroform, 0% to 50% EtOAc in hexanes over 40 mm using a 120g silica gel cartridge).The desired fractions were combined and concentrated to yield Intermediate 103A (1.7 g,7.33 mmol, 81 % yield) as an off-white solid. ?H NMR (400MHz, chloroform-d) 8.00(d, J9.0 Hz, 1H), 7.23 (d, J=2.6 Hz, 1H), 6.93 (dd, J=9.0, 2.6 Hz, 1H), 3.90 (s, 3H).LC-MS: method C, RT = 1.82 mm, MS (ESI) m/z: 231.9 and 233.9 (M+H)t

Reference： [1]Patent: WO2018/13774,2018,A1 .Location in patent: Page/Page column 469

55
[ 700-36-7 ]
[ 1679-18-1 ]
[ 1227469-86-4 ]

Yield	Reaction Conditions	Operation in experiment
78%	With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In ethanol; water; toluene; at 110℃;	One neck r.b.f was added (4-chlorophenyl) boronic acid(46.2 g, 295 mmol), <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong>(50 g, 227 mmol), Tetrakis (triphenylphosphine) palladium (0)(38.1 g, 11.3 mmol), NaHCO3 (38 g, 454 mmol), toluene / ethanol / water (800 ml / 160 ml / 160 ml)The mixture was refluxed at 110 & lt; 0 & gt; C.Extraction with MC and drying over MgSO4.After column packing HX: MC = 5: 1 packing, it was lowered to 4: 1 and the upper SIDE was removed. HX: MC = 3: 1 to obtain 4'-chloro-5-fluoro-2-nitro-1,1'-biphenyl (45 g, 78%).

Reference： [1]Patent: KR2018/60696,2018,A .Location in patent: Paragraph 0185-0189

56
[ 700-36-7 ]
N-(1-((1R,3s,5S,6r)-3-aminobicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide [ No CAS ]
4-chloro-N-(1-((1R,3s,5S,6r)-3-((5-fluoro-2-nitrophenyl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With sodium t-butanolate; ruphos; In 1,4-dioxane; at 65℃; for 2h;Inert atmosphere;	To a suspension of 2-bromo-4-fluoro-l -nitrobenzene (24.79 mg, 0.113 mmol) in dioxane (1025 mu) was added RuPhos pre-catalyst fourth generation (17.43 mg, 0.020 mmol), 2- dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (9.56 mg, 0.020 mmol), sodium tert- butoxide (49.2 mg, 0.512 mmol), and N-(l-((lR,3s,5S,6r)-3-aminobicyclo[3.1.0]hexan-6- yl)propyl)-4-chlorobenzamide (30 mg, 0.102 mmol). The solution was degassed with N2 for 2 minutes then stirred at 65C for 2 hours. The solution was concentrated and purified by mass- triggered preparative HPLC (Mobile phase: A = 0.1% TFA/H20, B = 0.1% TFA/MeCN; Gradient: B = [40] - [80]%; 12 min; Column: CI 8) to yield 4-chloro-N-(l-((lR,3s,5S,6r)-3- ((5-fluoro-2-nitrophenyl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide (9.2 mg, 0.021 mmol, 20% yield). MS (ES+) C22H23CIFN3O3 requires 431, found 432 [M+H]+.

Reference： [1]Patent: WO2018/136437,2018,A2 .Location in patent: Page/Page column 240; 241

57
[ 288-32-4 ]
[ 700-36-7 ]
1-(3-bromo-4-nitrophenyl)-1H-imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.6%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 48h;	[0225] To a solution of 2-bromo-4-fluoro-l -nitrobenzene (Intermediate 1, 1.00 g) in 25mL dry DMF was added imidazole (325 mg) and potassium carbonate (750 mg), and the mixture was stirred at room temperature for 2 days. The reaction mixture was poured into ice-water, filtered, and washed well with water. TLC: One spot only, Rf 0.50(5% MeOH in DCM). The wet light yellow solid was dissolved in hot EtOAc, filtered, dried/MgS04, stripped to 986mg light yellow solid. This material readily dissolved in DCM (~8mL) and was put on a 25g Silica (40-75u) cartridge, and chromatographed with 0-5%MeOH/DCM over 10 min; there was a small forerun, and l-(3-bromo-4-nitrophenyl)-lH-imidazole, 1-2, all came out from 6.5-8 min: 921mg (75.6% yield) after pumping.

Reference： [1]Patent: WO2018/191418,2018,A1 .Location in patent: Paragraph 0225

58
[ 700-36-7 ]
[ 5470-65-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydroxide; In water; at 95 - 105℃;	(3) Hydrolysis reaction, 700 mL of 15percent aqueous sodium hydroxide solution was added to the reaction flask, and the reaction temperature was controlled at 95 to 105 °C.160.4 g of the above nitro compound was added in portions, and the reaction was continued for a while, and the GC was followed until the reaction was completed.After a little cold, acidification, ice water water analysis, suction filtration, to obtain the target 150 g,The content is more than 98percent, and the yield is 98percent.

Reference： [1]Patent: CN109369411,2019,A .Location in patent: Paragraph 0009; 0012-0013; 0016

59
[ 446-51-5 ]
[ 700-36-7 ]
C₁₃H₉BrFNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With caesium carbonate; In N,N-dimethyl-formamide; at 50℃;Inert atmosphere;	A mixture of <strong>[446-51-5]2-fluorobenzyl alcohol</strong> (2.6 g, 20 mmol), 4-fluoro-2-bromonitrobenzene (4.4 g, 20 mmol), DMF (100 mL) and cesium carbonate (6.5 g, 20 mmol) was stirred under nitrogen atmosphere at 50C overnight. The reaction solution was evaporated under reduced pressure, diluted with (100 mL), extracted with ethyl acetate (300 mL x 3). The organic phase was combined, washed with saturated brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: PE:EA = 10/1) to give compound 55-d (3.3 g, 50 %). LC-MS (ESI): m/z = 326 [M+H]+.

Reference： [1]Patent: EP3492461,2019,A1 .Location in patent: Paragraph 0262; 0263

60
[ 446-51-5 ]
[ 700-36-7 ]
C₁₃H₁₁BrFNO [ No CAS ]

Reference： [1]Patent: EP3492461,2019,A1

61
[ 367-12-4 ]
[ 700-36-7 ]
2-bromo-4-(2-fluorophenoxy)-1-nitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 16h;Inert atmosphere;	According to route (E), 2-fluorophenol (1.8 g, 16 mmoles, 1 eq.) was placed in AA-dimethylformamide (50 mL) with K2CO3 (4.5 g, 32 mmoles, 2 eq.). Upon addition of 2-bromo-4-fluoro-l -nitrobenzene (3.5 g, 16 mmoles, 1 eq.), the reaction mixture was heated at 70C and stirred for 16 hours under an inert atmosphere of argon. Upon cooling to room temperature, the reaction mixture was partitioned between ethyl acetate and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgS04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to afford 2-bromo-4-(2-fluorophenoxy)-l- nitrobenzene (3.8 g, 77%). (0437) ?H NMR (300 MHz, CDCb) d 7.95 (d, j = 9.1 Hz, 1H), 7.30 - 7.15 (m, 5H), 6.95 (dd, j = (0438) 9.1, 2.6 Hz, 1H).

Reference： [1]Patent: WO2020/11810,2020,A1 .Location in patent: Page/Page column 68

62
[ 700-36-7 ]
[ 1730-25-2 ]
[ 883001-24-9 ]

Yield	Reaction Conditions	Operation in experiment
58%	In tetrahydrofuran; at -60℃; for 4h;Inert atmosphere;	To a solution of <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (0.5 g, 2.27 mmol, 1 eq.) in THF (20 mL) was added (E)-prop-1-en-1-ylmagnesium bromide (0.5 M in THF) (13.6 mL, 6.818 mmol, 3 eq) at -60 C. under nitrogen atmosphere. Then the reaction mixture was stirred at the same temperature for 4 h. The reaction was quenched with saturated ammonium chloride solution at -60 C. Then the resulting mixture was extracted with EtOAc (2*100 mL), washed with brine solution and concentrated under reduced pressure to give the crude product which was purified by flash column chromatography to afford 7-bromo-5-fluoro-3-methyl-1H-indole (0.3 g, 58%) as dense yellow liquid.
58%	In tetrahydrofuran; at -60℃; for 4h;	Step1: To a solution of <strong>[700-36-7]2-bromo-4-fluoro-1-nitrobenzene</strong> (0.5 g, 2.27 mmol, 1 eq.) in THF (20 mL) was added (E)-prop-1-en-1-ylmagnesium bromide (0.5 M in THF) (13.6 mL, 6.818 mmol, 3 eq) at -60C under nitrogen atmosphere. Then the reaction mixture was stirred at the same temperature for 4 h. The reaction was quenched with saturated ammonium chloride solution at -60G Then the resulting mixture was extracted with EtOAc (2 x 100 mL), washed with brine solution and concentrated under reduced pressure to give the crude product which was purified by flash column chromatography to afford 7-bromo-5-fluoro-3-methyl-1H-indole (0.3 g, 58%) as dense yellow liquid.

Reference： [1]Patent: US2020/24281,2020,A1 .Location in patent: Paragraph 0192-0194
[2]Patent: WO2020/16453,2020,A1 .Location in patent: Page/Page column 44

63
[ 700-36-7 ]
[3-amino-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone [ No CAS ]
[3-(5-fluoro-2-nitroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With methanesulfonato[9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene](2?-methylamino-1,1?-biphenyl-2-yl)palladium(ll); caesium carbonate; In 1,4-dioxane; at 90℃; for 2h;	General procedure: To a degassed suspension of compound Y (1 equiv.) in dioxane (0.1 M) were added a 2-bromo-nitrobenzene, cesium carbonate (2.4 equiv.) and XantPhos Pd G3 precatalyst (10 mol%). The reaction mixture was stirred 2h at 90C. The reaction mixture was diluted with DCM, washed with water, the aqueous layer was extracted with DCM. The combined organic layers were dried over sodium sulfate,concentrated. The resulting residue was purified by flash chromatography to afford the compound Z.

Reference： [1]Patent: WO2020/83878,2020,A1 .Location in patent: Page/Page column 149; 314-315

64
[ 62257-16-3 ]
[ 700-36-7 ]
5-(3-bromo-4-nitrophenoxy)-2-fluoroaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate; In dimethyl sulfoxide; at 85℃; for 2h;	To <strong>[62257-16-3]3-amino-4-fluorophenol</strong> (346mg, 2.727mmol) and 2-bromo-4-fluoro-1-nitrobenzene (600mg,2.727mmol) in DMSO (10ml) was added K2CD3 (1.13g, 8.182mmol).Stir the solution at 85C for 2 hoursAt this time, the solution was extracted with ethyl acetate, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and the filtrate was concentrated under reduced pressure to obtain a residueThe residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 7:1-6:1), and the resulting solution was concentrated under reduced pressureAfter shrinking, 760 mg of yellow solid was obtained, and the yield was 85%.

Reference： [1]Patent: CN112094248,2020,A .Location in patent: Paragraph 0124; 0127-0128

65
[ 700-36-7 ]
[ 3218-02-8 ]
3-bromo-N-(cyclohexylmethyl)-4-nitroaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium carbonate In dimethyl sulfoxide at 20℃; for 4h;	15 The synthesis of 3-bromo-N-(cyclohexylmethyl)-4-nitroaniline (217-1): To a solution of 215-1 (3.0 g, 12.4 mmol) in DMSO (20.0 mL) was added cyclohexylmethanamine (1.7 g, 15.0 mmol) and K2CO3 (3.6 g, 27.0 mmol).Then stirred the mixture for 4 h. After the reaction was completed, the reaction mixture was quenched with water, and extracted with EtOAc (20.0 mL x 3). The organic layers were washed with brine, dried over MgS04 and concentrated to give 217-1 (3.5 g, about 83 % yield) as an oil. MS Calcd.: 312.0; MS Found: 313.0 [M + H] +.

Reference： [1]Current Patent Assignee: SRI INTERNATIONAL INC - WO2021/133689, 2021, A2 Location in patent: Paragraph 00312

66
[ 700-36-7 ]
[ 536-74-3 ]
[ 199620-15-0 ]
[ 103914-44-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With anhydrous sodium carbonate; tri-tert-butylphosphonium hydrogen tetrafluoroborate In water monomer; N,N-dimethyl-formamide at 110℃; for 24h;

Reference： [1]Li, Chenyu; Li, Chuan-Ying; Lu, Wangyang; Wang, Jian-Shu; Wu, Xiao-Feng; Xu, Tiefeng; Ying, Jun [Journal of Catalysis, 2022, vol. 408, p. 81 - 87]

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Code	Phrase
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P103	Read label before use
Prevention
Code	Phrase
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P234	Keep only in original container.
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H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere