Name: 899436-71-6|(2-Methylpyridin-3-yl)boronic acid|98%
Brand: Ambeed
SKU: A212903
Rating: 91 (27 reviews)

1
[ 899436-71-6 ]
[ 807620-96-8 ]
3-[3-Fluoro-5-(5-pyridin-2-yl-tetrazol-2-yl)-phenyl]-2-methyl-pyridine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 5477 - 5480

2
[ 952402-43-6 ]
[ 899436-71-6 ]
[ 952402-46-9 ]

Yield	Reaction Conditions	Operation in experiment
56%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); CyJohnPhos; In 1,2-dimethoxyethane; water; for 3h;Heating / reflux;	Preparation 47: 3-Benzoyl- 1 -(4-chloro-butyl)-5-(2-methyl-pyridin-3-yl)-1 H- pyrimidine-2,4-dione (Prep47); 3-Benzoyl-1-(4-chloro-butyl)-5-iodo-1 H-pyrimidine-2,4-dione (Prep 44, 541 mg, 1.25 mmol) was dissolved in degassed DME-water solution (5-1 , 37.5 ml_). 2-Methy-pyridine 3- boronic acid (325 mg, 1.9 mmol), Na2CO3 (265 mg, 2.5 mmol), 2- (dicyclohexylphosphino)biphenyl (52 mg, 0.15 mmol) and Pd(PPh3)4 (288 mg, 0.25 mmol) were added and the mixture was refluxed for 3 hours. A second batch was run in parallel <n="89"/>in the same reaction conditions on 3-Benzoyl-1-(4-chloro-butyl)-5-iodo-1 H-pyrimidine-2,4- dione (Prep 44 , 108 mg, 0.25 mmol) using 2-Methy-pyridine 3-boronic acid (65 mg, 0.375 mmol), Na2CO3 (53 mg, 0.5 mmol), 2-(dicyclohexylphosphino)biphenyl (17.5 mg, 0.05 mmol) and Pd(PPh3)4 (57.75 mg, 0.05 mmol) dissolved in degassed DME-water solution (5-1 , 7.5 ml_). The crudes were then mixed and the solvents were evaporated under vacuum and the residue was partitioned between ethyl acetate and water. The organic phase was dried (Na2SO4) and evaporated; the crude was purified by flash chromatography with DCM-MeOH-NH4OH (98-2-0.2) and then loaded on SCX cartridge washing with MeOH and eluting with MeOH/NH3 95:5 to give the title compound (330 mg, 56% yield).MS (ES) (mlz): 398.5 [M+H]+.

Reference： [1]Patent: WO2007/113232,2007,A1 .Location in patent: Page/Page column 86-87

3
[ 952402-39-0 ]
[ 899436-71-6 ]
5-(2-methyl-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); CyJohnPhos; In 1,2-dimethoxyethane; water; at 90℃; for 14.5h;	Example 19: 5-(2-methyl-3-pyridinyl)-1 -(3-{(1 S,5/?)-1 -[4-(trifluoromethyl)phenyl]-3- azabicydo[3.1.0]hex-3-yl}propyl)-2,4(1W,3H)-pyrimidinedione dihydrochloride (E19); 5-lodo-1 -{3-[(1 S,5R)-1 -(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hex-3-yl]-propyl}-1 H- pyiotamidine-2,4-dione (Prep40, 100 mg, 0.2 mmol) was dissolved in degassed DME-water solution (6-1 , 3,5 ml_). 2-Methylpyridine-3-boronic acid (69 mg, 0.4 mmol), Na2CO3 (67 mg, 0.6 mmol), 2-(dicyclohexylphosphino)biphenyl (14 mg, 0.04 mmol) and Pd(PPh3)4 (46 mg, 0.04 mmol) were added and the mixture stirred for 12 hours at 900C. Fresh 2- (dicyclohexylphosphino)biphenyl (14 mg, 0.04 mmol) and Pd(PPh3)4 (46 mg, 0.04 mmol) were added and the reaction stirred at 900C for 2.5h.The reaction was diluted with ethyl acetate, and washed with water. The organic phase was dried (Na2SO4) and evaporated; the crude was purified by flash chromatography with DCM-MeOH-NH4OH (98-2-1 ) to give the free base of the title compound as a yellow solid (30 mg, 30% yield).

Reference： [1]Patent: WO2007/113232,2007,A1 .Location in patent: Page/Page column 142

4
[ 122213-94-9 ]
[ 73183-34-3 ]
[ 899436-71-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate;[1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); In N,N-dimethyl-formamide; at 80℃;Product distribution / selectivity;	Intermediate 1 5'-Bromo-2'-chloro-2-methyl-[3,4']bipyridinyl A mixture of 2.73 g (11.3 mmol) trifluoro-methanesulfonic acid 2-methyl-pyridin-3-yl ester, 3.16 g (12.4 mmol) bis(pinacolato)diboron, 3.33 g (33.9 mmol) potassium acetate and 0.46 g (0.56 mmol) dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct in 75 ml N,N-dimethylformamide was heated at 80 C. over night under argon. After cooling to room temperature 5.40 g (17.0 mmol) 5-bromo-2-chloro-4-iodo-pyridine, another portion of 0.46 g (0.56 mmol) dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct and 30 ml of a deoxygenated 2 M aqueous solution of sodium carbonate were added. The reaction mixture was heated at 80 C. for 4.5 h. After cooling to room temperature the mixture was diluted with water and extracted with three portions of tert-butyl methyl ether. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Flash column chromatography gave 1.00 (31%) of the title compound as a light yellow solid. MS m/e (%): 285 (M+H+, 100); A mixture of trifluoro-methanesulfonic acid 2-methyl-pyridin-3-yl ester, bis(pinacolato)diboron, potassium acetate and dichloro[1,1'-bis(diphenylphosphino)ferrocenelpalladium(II) dichloromethane adduct in N,N-dimethylformamide is heated at about 80 C. over night under argon. After cooling to room temperature 5-bromo-2-chloro-4-iodo-pyridine, another portion of dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct and a deoxygenated aqueous solution of sodium carbonate are added. The reaction mixture is heated at about 80 C. for 4.5 h. After cooling to room temperature the mixture is concentrated, dried and purified in conventional manner.

Reference： [1]Patent: US2006/189626,2006,A1 .Location in patent: Page/Page column 4-5; 10

5
[ 401892-47-5 ]
[ 899436-71-6 ]
[ 907182-59-6 ]

Yield	Reaction Conditions	Operation in experiment
31%	With sodium carbonate;[1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); In water; N,N-dimethyl-formamide; at 80℃; for 4.5h;Product distribution / selectivity;	Intermediate 1 5'-Bromo-2'-chloro-2-methyl-[3,4']bipyridinyl A mixture of 2.73 g (11.3 mmol) trifluoro-methanesulfonic acid 2-methyl-pyridin-3-yl ester, 3.16 g (12.4 mmol) bis(pinacolato)diboron, 3.33 g (33.9 mmol) potassium acetate and 0.46 g (0.56 mmol) dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct in 75 ml N,N-dimethylformamide was heated at 80 C. over night under argon. After cooling to room temperature 5.40 g (17.0 mmol) 5-bromo-2-chloro-4-iodo-pyridine, another portion of 0.46 g (0.56 mmol) dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct and 30 ml of a deoxygenated 2 M aqueous solution of sodium carbonate were added. The reaction mixture was heated at 80 C. for 4.5 h. After cooling to room temperature the mixture was diluted with water and extracted with three portions of tert-butyl methyl ether. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Flash column chromatography gave 1.00 (31%) of the title compound as a light yellow solid. MS m/e (%): 285 (M+H+, 100); A mixture of trifluoro-methanesulfonic acid 2-methyl-pyridin-3-yl ester, bis(pinacolato)diboron, potassium acetate and dichloro[1,1'-bis(diphenylphosphino)ferrocenelpalladium(II) dichloromethane adduct in N,N-dimethylformamide is heated at about 80 C. over night under argon. After cooling to room temperature 5-bromo-2-chloro-4-iodo-pyridine, another portion of dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct and a deoxygenated aqueous solution of sodium carbonate are added. The reaction mixture is heated at about 80 C. for 4.5 h. After cooling to room temperature the mixture is concentrated, dried and purified in conventional manner.

Reference： [1]Patent: US2006/189626,2006,A1 .Location in patent: Page/Page column 4-5; 10

6
[ 38749-79-0 ]
[ 899436-71-6 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 3-bromo-2-methylpyridine (4.00 g, 23 mmol), triisopropyl borate (6.40 mL, 28 mmol) in 50 mL of 4/1 toluene/THF (4/1, 50 mL) at -78 C. was added was added butyllithium (17 mL, 28 mmol), dropwise. The mixture was allowed to warm up to 30 min at -70 C. LCMS and then to 20 C. HCl (2M) was added to bring the solution to pH1. Then water (20 mL) was added and the mixture was extracted with toluene. The aqueous layer was neutralized with 1 M NaOH and extracted with dichloromethane. The aqueous layer was concentrated to dryness and the white solid was washed with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated to give 2.10 g of 2-methylpyridin-3-ylboronic acid as a yellow oil. ES+=138.2 (M+H)

Reference： [1]Patent: US2006/199817,2006,A1 .Location in patent: Page/Page column 50
[2]British Journal of Pharmacology,2018,vol. 175,p. 3470 - 3485

7
[ 1279106-45-4 ]
[ 899436-71-6 ]
[ 1279106-46-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 100℃; for 18h;Inert atmosphere;	To a solution of 5-(4-Methyl-2-phenyl-thiazol-5-yl)-2-trifluoromethanesulfonyloxy-indole-1-carboxylic acid ethyl ester (30 mg, 0.061 mmol) and <strong>[899436-71-6]2-methylpyridine-3-boronic acid</strong> (9 mg, 0.067 mmol) in toluene (0.67 mL) was added EtOH (0.44 mL) followed by sat. NaHCO3 (0.30 mL). The mixture was purged with nitrogen (20 min), and then Pd(PPh3)4 (10 mol %, 7 mg) was added. After stirring for 18 h at 100 C. the mixture was filtered through Celite and EtOAc was added (30 mL). This mixture was washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography (40% EtOAc-Hexane) to give 5-(4-Methyl-2-phenyl-thiazol-5-yl)-2-(2-methyl-pyridin-3-yl)-indole-1-carboxylic acid ethyl ester (13 mg).

Reference： [1]Patent: US2011/71150,2011,A1 .Location in patent: Page/Page column 50

8
[ 1192152-59-2 ]
[ 899436-71-6 ]
[ 1252573-32-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 3h;Inert atmosphere; Microwave irradiation;	Compound 6: N-[7-(2-methyl-3-pyridinyl)-2-(trifluoromethyl)-1H-indol-5-yl]methyl}-6-(trifluoromethyl)-3-pyridinecarboxamide; In a 2 mL microwave vial N-[(2-Trifluoromethyl-7-bromo-1H-indol-5-yl)methyl]-5-(trifluoromethyl)-2-pyridinecarboxamide (Intermediate 6, 100 mg), <strong>[899436-71-6]2 methylpyridine-3-boronic acid</strong> (Apollo Scientific Ltd., 88 mg), sodium carbonate (114 mg) and tetrakis(triphenylphosphine)palladium(0) (24.79 mg) were stirred in 1,4-Dioxane (2 mL)/Water (0.5 mL) and de-gassed using argon gas. The reaction mixture was then heated in a microwave reactor at 100 C. for 3 h. The reaction mixture was poured into water (20 mL) and extracted with ethyl acetate (40 mL). The organic extract was then washed with water (2×20 mL), dried (MgSO4), filtered and the solvent removed. The resulting residues were purified by MDAP and evaporated to dryness to give the title compound as a white solid (59 mg).m/z (ES+) 479 (M+1); 1H NMR (400 MHz, d6-DMSO): delta 11.98 (1H, s), 9.50 (1H, t), 9.21 (1H, s), 8.58 (1H, m), 8.51 (1H, dd), 8.07 (1H, d), 7.70 (1H, s), 7.65 (1H, dd), 7.39-7.32 (1H, m), 7.16 (1H, s), 7.09 (1H, s), 4.69 (2H, d), 2.24 (3H, s).

Reference： [1]Patent: US2012/136009,2012,A1 .Location in patent: Page/Page column 14

9
[ 1310032-06-4 ]
[ 899436-71-6 ]
C₁₇H₁₄ClN₇ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4967 - 4974

10
C₁₄H₁₁BrClN₅O [ No CAS ]
[ 899436-71-6 ]
C₂₀H₁₇ClN₆O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4967 - 4974

11
[ 1159795-35-3 ]
[ 899436-71-6 ]
C₁₇H₁₅FN₄O₃ [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 5876 - 5884,9

12
[ 1224884-70-1 ]
[ 899436-71-6 ]
[ 1224884-74-5 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 5876 - 5884,9

13
[ 1422169-87-6 ]
[ 899436-71-6 ]
[ 1422169-88-7 ]

Yield	Reaction Conditions	Operation in experiment
57%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In ethanol; toluene; at 80℃; for 3h;Inert atmosphere;	To a solution of 2-bromobenzofuran-5-carbonitrile (100 mg, 0.45 mmol) in toluene (3 mL) and EtOH (3 mL) was added <strong>[899436-71-6]2-methylpyridine-3-boronic acid</strong> (74 mg, 0.54 mmol) and the solution was purged with Ar for 10 min. A solution of Na2C03 (143 mg, 1.3 mmol) in water (8 mL) and catalytic Pd(dppf)Cl2,CH2Cl2 (36 mg, 0.04 mmol) were added and the reaction mixture was heated to 80 C for 3 h. The reaction mixture was cooled to rt and solvent was removed under reduced pressure. The resultant residue was diluted with EtO Ac, washed with water and brine, dried over anhydrous Na2S04, filtered, and concentrated under reduced pressure. The resultant residue was purified by column chromatography (25% EtO Ac/petroleum ether) to afford the title compound (60 mg, 57%). TLC: 50% EtOAc/petroleum ether, Rf= 0.3. H NMR (400 MHz, CDC13) delta ppm 8.58 (dd, J = 4.8, 1.6 Hz, 1H), 8.16 (dd, J = 7.9, 1.7 Hz, 1H), 8.00 (m, 1H), 7.64 (m, 2H), 7.31 (dd, J = 8.0, 4.8 Hz, 1H), 7.06 (s, 1H), 2.85 (s, 3H).

Reference： [1]Patent: WO2013/19682,2013,A1 .Location in patent: Page/Page column 110; 111

14
[ 1422169-92-3 ]
[ 899436-71-6 ]
[ 1422167-08-5 ]

Yield	Reaction Conditions	Operation in experiment
17.8%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; at 90℃; for 3h;Inert atmosphere;	A solution of 2-(2-bromobenzofuran-5-yl)-N-((4-chloro-2-methylphenyl)(phenyl)methyl)- 2-hydroxyacetamide (200 mg, 0.41 mmol), <strong>[899436-71-6]2-methylpyridin-3-ylboronic acid</strong> (56.2 mg, 0.41 mmol), Pd(dppf)Cl2 (33.5 mg, 0.041 mmol), and K2C03 (1 13 mg, 0.82 mmol) in 1 ,4-dioxane (10 mL) and water (2 mL) was stirred under Ar at 90 C for 3 h. Water (10 mL) was added and the reaction mixture was extracted with EtO Ac (3 x 10 mL). The combined organic layers were washed with brine, dried over Na2S04, filtered, and concentrated. The resultant residue was purified by preparative HPLC to obtain the title compound (31 mg, 17.8%). LCMS-P 1 : 497[M+H]+; Rt: 1.618 min. 1H NMR (500 MHz, DMSO-d6) delta ppm 8.52 (s, 1H), 8.30 (s, 1H), 7.57 - 7.19 (m, 7H), 7.08 - 6.80 (m, 7H), 6.27 - 6.22 (m, 1H), 5.16 (d, J= 8.5 Hz, 1H), 2.78(d, J= 6.0 Hz, 3H), 2.10 (d, J = 16.5 Hz, 3H).

Reference： [1]Patent: WO2013/19682,2013,A1 .Location in patent: Page/Page column 112; 113

15
[ 943541-43-3 ]
[ 899436-71-6 ]
[ 1422169-98-9 ]

Yield	Reaction Conditions	Operation in experiment
110 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; acetonitrile; at 100℃; for 3h;Inert atmosphere; Sealed tube;	Methyl 2-(2-chloroquinolin-6-yl)acetate (100 mg, 0.42 mmol), <strong>[899436-71-6]2-methylpyridine-3-boronic acid</strong> (93 mg, 0.42 mmol), and Na2C03 (225 mg, 2.12 mmol) were dissolved in 3 : 1 CH3CN/H20 (10 mL) and the solution was purged with Ar for 10 min. Pd(PPh3)4 (25 mg, 0.02 mmol) was added and the reaction mixture was heated to 100 C for 3 h in a sealed tube. The reaction mixture was cooled to rt, diluted with water, and extracted with EtO Ac. The organic layer was washed with water and brine, dried over anhydrous Na2SO/t, filtered, and concentrated under reduced pressure to afford the title compound (1 10 mg). TLC: 50% EtOAc/petroleum ether, R = 0.2.

Reference： [1]Patent: WO2013/19682,2013,A1 .Location in patent: Page/Page column 118

16
[ 1422170-05-5 ]
[ 899436-71-6 ]
[ 1422170-06-6 ]

Yield	Reaction Conditions	Operation in experiment
67%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Inert atmosphere; Microwave irradiation;	A solution of ethyl 2-(2-bromobenzo[<i]thiazol-6-yl)acetate (240 mg, 0.8 mmol), 2- methylpyridine-3-boronic acid (164 mg, 1.2 mmol), Pd(dppf)Cl2 (71 mg, 0.096 mmol), and K2C03 (331 mg, 2.4 mmol) in 1,4-dioxane (3 mL) and water (1.5 mL) under Ar was heated under microwave irradiation at 1 10 C for 30 min. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3 x 10 mL), washed with brine, dried over Na2SO/t, filtered, and concentrated. The resultant residue was purified by column chromatography (33%EtOAc/petroleum ether) to obtain the title compound (168 mg, 67%). LCMS-P1 : 313.0 [M+2H]+; Rt: 1.66 min.

Reference： [1]Patent: WO2013/19682,2013,A1 .Location in patent: Page/Page column 121

17
[ 193290-19-6 ]
[ 899436-71-6 ]
[ 1428761-04-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In tetrahydrofuran; water; toluene; at 90℃; for 15h;Inert atmosphere;	To a solution of methyl 2-(4-bromo-2-fluorophenyl) acetate (1 g, 4.05 mmol) in toluene/THF H20 (15 mL, v/v/v=2/2/l ) were added <strong>[899436-71-6]2-methylpyridin-3-ylboronic acid</strong> (870 mg, 3.97 mmol), AcO (790 mg, 8.05 mmol) and PdCl2(dppf) (222 mg, 0.31 mmol) under nitrogen. The reaction mixture was stirred at 90C for 15 h. The reaction mixture was filtered, the filtrate was washed with water, extracted with EtOAc (2 x 10 mL). The combined layers were washed with brine, dried over Na2S04 and concentrated. The residue was purified by column chromatography on silica gel eluted with 0- 10% EtOAc in petroleum ether to afford the desired product (0.9 , 86%). LCMS m/z 260 (M+l )+.

Reference： [1]Patent: WO2013/43232,2013,A2 .Location in patent: Paragraph 00605; 00652

18
[ 1429752-96-4 ]
[ 899436-71-6 ]
[ 1429752-45-3 ]

Reference： [1]Patent: WO2013/52395,2013,A1 .Location in patent: Page/Page column 61; 62

19
[ 1564236-44-7 ]
[ 899436-71-6 ]
[ 1564224-81-2 ]

Yield	Reaction Conditions	Operation in experiment
10%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Microwave irradiation;	K2CO3 (28.1 mg, 0.204 mmol), <strong>[899436-71-6]2-methylpyridin-3-ylboronic acid</strong> (22.3 mg, 0.163 mmol) and Pd(Ph3P)4 (9.41 mg, 0.008 mmol) were each added sequentially to the microwave reaction vial. A solution of the compound from example 2.1(30 mg, 0.08mmol) in 3 mL of dioxane and 0.5 mL of H20 was injected into the reaction vial. The reaction was heated in a Biotage microwave at 100C for 1 hr. The reaction mixture was filtered and concentrated to dryness to give a brown solid, which was purified by preHPLC to give 2.5 mg of the title compound (yield: 10%).LC-MS: m/z 332 (M+H); RT=1.30 min/2.5 min. 1H NMR (400 MHz, d6-DMSO): delta = 8.81 (s, 1H), 8.17 (s, 1 H), 7.937.87 (m, 1 H), 7.66 (d, J=4.8 Hz,1H), 7.15-7.13 (m, 1 H), 4.45 (s, 3 H), 2.45 (s, 3 H).

Reference： [1]Patent: WO2014/27078,2014,A1 .Location in patent: Page/Page column 60
[2]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 406 - 412

20
[ 1564237-50-8 ]
[ 899436-71-6 ]
[ 1564226-35-2 ]

Yield	Reaction Conditions	Operation in experiment
19%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Microwave irradiation;	The K2CO3 (54 mg, 0.236 mmol), <strong>[899436-71-6]2-methylpyridin-3-ylboronic acid</strong> (36 mg, 0.26 mmol) and Pd(Ph3P)4 (30 mg, 0.025 mmol) were each added sequentially to themicrowave reaction vial. A solution of the compound from example 5.i (50 mg, 0.i3i mmol) in 2 mL of dioxane and 0.5 mL of H2O was injected into the reaction vial. The reaction was heated in a Biotage microwave at iOOC for ihr. The reaction mixture was filtered and concentrated to give a brown solid, which was purified by HPLC to give 8 mg of the title compound (yield: 19%).LC-MS: m/z 324 (M+H); RT=1.53 min/2.5 min. 1H NMR (400 MHz, d6-DMSO): delta = 8.718.69 (m, 1H), 7.947.91 (m, 1H),7.497.46(m, 1H),7.30(dd,J=11.6, 2.4 Hz, iH), 6.64 (dd,J=11.6, 2.4 Hz, 1H),4.50 (s, 3 H), 4.14 (s, 3 H), 2.35 (s, 3 H).

Reference： [1]Patent: WO2014/27078,2014,A1 .Location in patent: Page/Page column 62; 63
[2]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 406 - 412

21
[ 1611002-24-4 ]
[ 899436-71-6 ]
[ 1611000-74-8 ]

Yield	Reaction Conditions	Operation in experiment
33.1%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere;	The compound of example 263 (0.300 g, 0.993 mmol) was treated with (2- methoxypyridin-3-yl)boronic acid (0.167 g, 1 .092 mmol) in the presence of dichlorobis(triphenylphosphine) palladium(ll) (0.012 g, 0.016 mmol) and potassium carbonate (0.206 g, 1 .489 mmol) in DMF according to the procedure for the preparation of the compound of example 2 to afford the title compound. Yield : 0.1 10 g (33.1 %); 1 H NMR (DMSO-d6, 300 MHz): delta 2.26 (s, 3H, CH3), 2.5 (s, 3H, CH3), 3.9 (s, 3H, OCH3), 7.1 1 -7.15 (dd, 1 H, J=5.1 Hz & J=7.2 Hz, Ar), 7.32-7.35 (d, 1 H, J=7.8 Hz, Ar), 7.61 (s, 1 H, Ar), 7.68 (s, 1 H, Ar), 7.75-7.78 (dd, 1 H, J=1 .5 Hz & J=7.8 Hz, Ar), 7.89-7.90 (m, 2H, Ar), 8.2 (d, 1 H, J=3.3 Hz, Ar), 8.4 (d, 1 H, J=1 .5 Hz, Ar); MS (ES+): m/e 331 .2 (M+1 ).

Reference： [1]Patent: WO2014/80241,2014,A1 .Location in patent: Page/Page column 128

22
[ 6188-23-4 ]
[ 899436-71-6 ]
[ 1611001-25-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere;	The compound of example 1 (0.195 g, 0.990 mmol) was treated with (2-methylpyridin-3- yl)boronic acid (0.176 g, 1.28 mmol) in the presence of dichlorobis(triphenylphosphine)palladium(ll) (0.011 g, 0.016 mmol) and potassium carbonate (0.205 g, 1.48 mmol) according to the procedure for the preparation of the compound of example 2 to afford the title compound. Yield: 0.2 g (95 %); MS (ES+): m/e 210 (M+1).

Reference： [1]Patent: WO2014/80241,2014,A1 .Location in patent: Page/Page column 58

23
[ 1616828-53-5 ]
[ 899436-71-6 ]
[ 1616831-37-8 ]

Yield	Reaction Conditions	Operation in experiment
0.1 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; at 130℃; for 0.5h;Microwave irradiation;	a) 8-Methoxy-6- (2-methylpyridin-3-yl)guinazolin-4(3H)-oneA mixture of 6-bromo-8-methoxyquinazolin-4(3H)-one (0.15 g, 0.588 mmol), <strong>[899436-71-6]2-methylpyridin-3-ylboronic acid</strong> (0.12 g, 0.882 mmol), dichloro- 1,1 ?-bis (diphenylphosphino)ferrocenepalladium(II) (0.01 g, 0.12 mmol) and cesium carbonate (0.38 g, 1.18 mmol) in dioxane (2m1) / water (0.2 ml) was heated in a microwave oven for 30 mm at 130 C. The reaction mixture was poured on water and extracted with dichloromethane. The crude product was purified by chromatography (silica gel, ethyl acetate/methanol= 100:0 to 70:30) to give the title compound (0.10 g) as a light brown solid. MS: mle = 268.2 [M+Hf?.

Reference： [1]Patent: WO2014/102233,2014,A1 .Location in patent: Page/Page column 146

24
[ 53180-92-0 ]
[ 899436-71-6 ]
5-(2-methylpyridin-3-yl)pyridazin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; at 140℃; for 1h;	Preparation 9.2: 5-(2-methylpyridin-3-yl)pyridazin-4-amine 7v [00288] A mixture of <strong>[53180-92-0]5-chloropyridazin-4-amine</strong> (50 mg, 0.386 mmol), (2-methyl-3- pyridyl)boronic acid (63.43 mg, 0.463 mmol), palladium triphenylphosphane (22.3 mg, 0.0193 mmol) and a2C03 (386 mu^ of 2M, 0.772 mmol) in dioxane (2 mL) was heated at 140C for lh. The mixture was then cooled to room temperature and partitioned between DCM and water. The organic layer was filtered through a SCX column, eluting with a 2M solution of H3 in MeOH. The eluate was concentrated in vacuo to give the title compound 7v (72 mg, 100% Yield).

Reference： [1]Patent: WO2014/143241,2014,A1 .Location in patent: Paragraph 00287-00288

25
4-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one [ No CAS ]
[ 899436-71-6 ]
4-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-methyl-2-(2-methylpyridin-3-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4%	With pyridine; ammonium cerium (IV) nitrate; copper diacetate; at 65℃; for 1.16667h;Molecular sieve; Inert atmosphere;	Example 81 4-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-methyl-2-(2-methylpyridin-3-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one To a stirred solution of 4-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Step 81.1) (200 mg, 0.542 mmol) in CAN (4 mL) with molecular sieves (4 g) under Ar were added <strong>[899436-71-6]2-methylpyridine-3-boronic acid</strong> (166 mg, 1.085 mmol), pyridine (0.088 mL, 1.085 mmol) and copper(II) acetate (148 mg, 0.813 mmol) and the reaction mixture was stirred 10 min at 65 C. <strong>[899436-71-6]2-methylpyridine-3-boronic acid</strong> (1.485 g, 10.85 mmol) was added portionwise over a period of 1 hr. The reaction mixture was concentrated under reduced pressure, quenched with a saturated aq. NaHCO3 solution and the aq. layer was extracted with CH2Cl2. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2/MeOH 1.5-5%). followed by preparative achiral SFC (column 4-Ethyl-pyridine, gradient 13-18% in 6 min_total 11 min) and triturated in Hexane/Et2O (1:1) to afford the title product (11 mg, 0.024 mmol, 4% yield). tR: 3.20 min (HPLC 1); tR: 0.87 min (LC-MS 2); ESI-MS: 460 [M+H]+ (LC-MS 2); Rf=0.53 (CH2Cl2/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) delta ppm 1.89 (s, 3H) 1.93 (s, 3H) 2.18 (s, 3H) 3.37 (s, 3H) 6.23 (s, 1H) 7.28-7.49 (m, 6H) 7.77 (d, J=2.7 Hz, 1H) 7.88 (dd, J=7.8, 1.56 Hz, 1H) 8.63 (dd, J=4.9, 1.4 Hz, 1H).
4%	With pyridine; ammonium cerium (IV) nitrate; copper diacetate; at 65℃; for 1.33333h;Inert atmosphere; Molecular sieve;	To a stirred solution of 4-(4-chlorophenyl)-5-(1 ,5-dimethyl-6-oxo-1 ,6-dihydropyridin-3-yl)-3- methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Step 81.1) (200 mg, 0.542 mmol) in CAN (4 mL) with molecular sieves (4 g) under Ar were added <strong>[899436-71-6]2-methylpyridine-3-boronic acid</strong> (166 mg, 1.085 mmol), pyridine (0.088 mL, 1.085 mmol) and copper(ll) acetate (148 mg, 0.813 mmol) and the reaction mixture was stirred 10 mm at 65 C. <strong>[899436-71-6]2-methylpyridine-3-boronic acid</strong> (1.485 g,10.85 mmol) was added portionwise over a period of 1 hr. The reaction mixture was concentrated under reduced pressure, quenched with a saturated aq. NaHCO3 solution and the aq. layer was extracted with CH2CI2. The combined organic layers were dried over Na2504 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2CI2/MeOH 1.5-5%). followed by preparative achiral SF0 (column 4-Ethyl-pyridine, gradient 13-18% in 6 mm_total ii mm) and triturated in Hexane/Et20 (1:1) to afford the title product (11 mg, 0.024 mmol, 4% yield). tR. 3.20 mm (HPLC 1); tR. 0.87 mm (LC-MS 2); ESIN MS: 460 [M+H] (LC-MS 2); R= 0.53 (CH2CI2/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) O ppm 1.89 (s, 3 H) 1.93 (s, 3 H) 2.18 (s, 3 H) 3.37 (s, 3 H) 6.23 (s, 1 H) 7.28- 7.49 (m, 6 H) 7.77 (d, J=2.7 Hz, 1 H) 7.88 (dd, J=7.8, 1.56 Hz, 1 H) 8.63 (dd, J=4.9, 1.4 Hz, 1 H).

Reference： [1]Patent: US2014/349990,2014,A1 .Location in patent: Paragraph 0923; 0924
[2]Patent: WO2014/191896,2014,A1 .Location in patent: Page/Page column 188; 189

26
4-(2-cyclopropyl-4-iodo-1H-benzo [d]imidazol-6-yl)-3,5-dimethylisoxazole [ No CAS ]
[ 76-05-1 ]
[ 899436-71-6 ]
4-(2-cyclopropyl-7-(2-methylpyridin-3-yl)-1H-benzo[d]imidazol-5-yl)-3,5-dimethylisoxazole trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a 0.5 to 2 mL Smith process vial equipped with a stir bar was added <strong>[899436-71-6]2-methylpyridin-3-ylboronic acid</strong> (0.45 mmol, 62 mg), 4-(2-cyclopropyl-4-iodo-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole (37.9 mg, 0.1 mmol) (Example 8, Step 4), potassium carbonate (0.90 mmol, 125 mg), and PEPPSI-IPr catalyst (0.01 mmol, 6.8 mg). The reaction vessel was capped with a rubber septum, evacuated and backfilled three times with N2, followed by the addition of 1,4-dioxane (0.4 mL) and water (0.1 mL). The reaction mixture was then heated in a microwave reactor for 30 minutes at 130 C. The organic layer was then removed by syringe, filtered, and directly injected for purification by preparative reverse phase high performance liquid chromatography (Phenomenex Gemini C18 column, 5% to 50% gradient acetonitrile in water with 0.1% TFA) to give 4-(2-cyclopropyl-7-(2-methylpyridin-3-yl)-1H-benzo[d]imidazol-5-yl)-3,5-dimethylisoxazole as a TFA salt. C21H20N4O. 345.2 (M+1). 1H NMR (400 MHz, CD3OD) delta 8.81 (dd, J=5.7, 1.5 Hz, 1H), 8.43 (dd, J=7.9, 1.5 Hz, 1H), 7.93 (dd, J=7.8, 5.8 Hz, 1H), 7.70 (d, J=1.4 Hz, 1H), 7.42 (d, J=1.5 Hz, 1H), 2.62 (s, 3H), 2.47 (s, 3H), 2.45-2.34 (m, 1H), 2.31 (s, 3H), 1.53-1.42 (m, 2H), 1.39-1.31 (m, 2H)

Reference： [1]Patent: US2014/336190,2014,A1 .Location in patent: Paragraph 0322; 0323; 0324

27
6-chloro-3-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-1,2,4-triazine-5-amine [ No CAS ]
[ 899436-71-6 ]
3-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-(2-methylpyridin-3-yl)-1,2,4-triazine-5-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; tricyclohexylphosphine; In 1,4-dioxane; water; at 140 - 150℃; for 1.16667h;Inert atmosphere; Microwave irradiation;	Example 2 3-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-(2-methylpyridin-3-yl)-1,2,4-triazine-5-amine Under an argon atmosphere, 140 mg (purity 65%, 0.256 mmol) of 6-chloro-3-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-1,2,4-triazine-5-amine were suspended in 5 ml of absolute dioxane. 105 mg (0.767 mmol) of <strong>[899436-71-6](2-methylpyridin-3-yl)boronic acid</strong>, 1.023 ml (1.023 mmol) of 1N aqueous potassium carbonate solution, and 14 mg (0.051 mmol) of tricyclohexylphosphine were added and argon was passed through the suspension with stirring. Then, 28 mg (0.038 mmol) of 1,1'-bis(diphenylphosphino)ferrocenepalladium(II) chloride were added and the reaction mixture was stirred for 30 min in the microwave at 140 C. Again, 19 mg (0.026 mmol) of 1,1'-bis(diphenylphosphino)ferrocenepalladium(II) chloride were added and the reaction mixture was stirred for 40 min in the microwave at 150 C. After cooling, the mixture was filtered over an Extrelut cartridge and after-washed with a mixture of dichloromethane/methanol (v/v=20:1). The filtrate was concentrated and the residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 20:80?100:0). 26 mg of the target compound were obtained (18% of theory). LC-MS (Method 4): Rt=4.27 min; MS (ESIpos): m/z=413 (M+H)+1H NMR (400 MHz; DMSO-d6): delta [ppm]=2.48 (s, 3H), 5.91 (s, 2H), 7.17 (t, 1H), 7.22-7.27 (m, 2H), 7.35-7.41 (m, 1H), 7.49 (dd, 1H), 7.68 (t, 1H), 8.14 (d, 1H), 8.73 (dd, 1H), 8.77 (d, 1H), 8.95 (dd, 1H).

Reference： [1]Patent: US2015/94308,2015,A1 .Location in patent: Paragraph 0295-0297

28
tert-butyl (3-bromo-5-methylpyrazolo[1,5-a]pyrimidin-7-yl)(pyridin-2-ylmethyl)carbamate [ No CAS ]
[ 899436-71-6 ]
3-(2-fluoropyridin-3-yl)-5-methyl-N-(pyridin-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%		General procedure: To a solution of 12 (1 equiv) in dioxane and water (5:1) was added boronic acid (1.2 equiv) followed by addition of cesium carbonate (1 equiv) and PdCl2(dffp) (0.1 equiv). The reaction mixture was degassed and heated at 80C overnight. The reaction was diluted with EtOAc and washed with water (2). After drying over Na2SO4, filtration and concentration, the crude product was dissolved in DCM (4 ml) and TFA (8 ml) was added. The reaction was stirred for 4 h at rt followed by concentration. The residue was dissolved in DCM and washed with 10% Na2CO3 (2), the organic layer was dried (MgSO4), filtered and concentrated. The crude product was purified by flash column chromatography (80% EtOAc/Hex) or recrystallization from DCM/Hexane or by prep TLC (EtOAc) to give the desired product

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 7240 - 7250

29
[ 899436-71-6 ]
[ 1585223-91-1 ]

Reference： [1]Patent: WO2015/148854,2015,A1
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 2054 - 2066

30
[ 899436-71-6 ]
methyl 3-(3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-7-(2-methylpyridin-3-yl)-1H-indole-2-carboxamido)benzoate [ No CAS ]

Reference： [1]Patent: WO2015/148854,2015,A1

31
[ 899436-71-6 ]
3-(3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-7-(2-methylpyridin-3-yl)-1H-indole-2-carboxamido)benzoic acid [ No CAS ]

Reference： [1]Patent: WO2015/148854,2015,A1

32
[ 899436-71-6 ]
3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-7-(2-methylpyridin-3-yl)-N-(3-(((4-nitrophenyl)sulfonyl)carbamoyl)phenyl)-1H-indole-2-carboxamide [ No CAS ]

Reference： [1]Patent: WO2015/148854,2015,A1

33
[ 1585223-50-2 ]
[ 899436-71-6 ]
[ 1585223-90-0 ]

Yield	Reaction Conditions	Operation in experiment
59 mg	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In 1,2-dimethoxyethane; ethanol; at 120℃; for 0.416667h;Inert atmosphere; Microwave irradiation;	A solution of ethyl 7-bromo-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-lH-indole- 2- carboxylate (60 mg, 0.129 mmol), <strong>[899436-71-6](2-methylpyridin-3-yl)boronic acid</strong> (20 mg, 0.15 mmol), Pd(PPh3)4 (7.46 mg, 6.45 muiotaetaomicron) and CsF (58.8 mg, 0.387 mmol) in ethanol (0.22 ml) and DME (0.44 ml) was degassed under Argon for 10 min. The mixture was then heated to 120 C in Biotage Initiator for 25 min. The reaction mixture was concentrated under vacuum, and the residue was purified by flash chromatography (Combi-flash Rf Hexane/EtOAc gradient 0-15%) to yield the title compound (59 mg). MS(ES) 477.3 (M+H).

Reference： [1]Patent: WO2015/148854,2015,A1 .Location in patent: Paragraph 00458
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 2054 - 2066

34
[ 899436-71-6 ]
C₂₆H₂₄Cl₂N₂O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 2054 - 2066

35
[ 899436-71-6 ]
[ 1585223-89-7 ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 2054 - 2066

36
[ 899436-71-6 ]
6-chloro-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-7-(2-methylpyridin-3-yl)-N-(phenylsulfonyl)-1H-indole-2-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 2054 - 2066

37
ethyl 7-bromo-6-chloro-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-1H-indole-2-carboxylate [ No CAS ]
[ 899436-71-6 ]
C₂₈H₂₈Cl₂N₂O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 2054 - 2066

38
1-[(1S)-5-bromo-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl]-2-(2,6-dichlorophenyl)ethanone [ No CAS ]
[ 899436-71-6 ]
2-(2,6-dichlorophenyl)-1-[(1S)-1-methyl-5-(2-methylpyridin-3-yl)-3,4-dihydroisoquinolin-2(1H)-yl]ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 115℃; for 1.5h;Sealed tube; Inert atmosphere; Microwave irradiation;	C.6. Method C. Synthesis of 2-(2,6-dichlorophenyl)-1-[5-(3,5-dimethyl-1 , 2-oxazol-4-yl)-1 - meth l-3,4-dihydroisoquinolin-2(1 H)-yl]ethanone 31. 1-(5-Bromo-1-methyl-3,4-dihydroisoquinolin-2(1 H)-yl)-2-(2,6-dichlorophenyl)ethanone a69 (50 mg, 0.12 mmol), 3,5-dimethylisoxazole-4-boronic acid (25 mg, 0.18 mmol) and K2C03 (51 mg, 0.36 mmol) were dissolved in 1 ,4-dioxane (3 mL) in a tube under argon. Tetrakis(triphenylphosphine)palladium(0) (14 mg, 0.01 mmol) was added. The tube was sealed and heated at 130 C during 1.5 h under microwave irradiation. The reaction mixture was concentrated under vacuum. The residue was diluted with EtOAc, sonicated, stirred, filtered, washed twice with EtOAc then concentrated under vacuum. The residue was purified by reverse phase chromatography (basic mode, LCMS prep) then triturated in Et20 to yield 14 mg of 2-(2,6-dichlorophenyl)-1-[5-(3,5-dimethyl-1 ,2-oxazol-4-yl)-1-methyl-3,4- dihydroisoquinolin-2(1 H)-yl]ethanone 31 as a yellow solid. Yield: 27%. LCMS (ES+): 429/431/433 (M+H)+, 100% purity. 2-(2,6-dichlorophenyl)-1 -[(1 S)-1 -methyl-5-(2-m 2(1 H)-yllethanone 143 LCMS (ES+): 425/427/429 (M+H)+, 91 % purity.

Reference： [1]Patent: WO2016/55479,2016,A1 .Location in patent: Page/Page column 114-115; 116-117

39
6-allyl-N-(1-(6-chloropyrimidin-4-yl)piperidin-4-yl)-N,2-dimethyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-4-carboxamide [ No CAS ]
[ 899436-71-6 ]
6-allyl-N,2-dimethyl-N-[1-[6-(2-methyl-3-pyridyl)pyrimidin-4-yl]-4-piperidyl]-7-oxo-1H-pyrrolo[2,3-c]pyridine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 85℃; for 0.5h;Microwave irradiation;	A mixture of 6-aIlyl-N-( 1 -(6-chloropyrimidin-4-yl)piperidin-4-yl)-N,2-dimethyi-7-oxo- 6,7- dihydro-lH-pyrrolo[253-c]pyridine-4-carboxamide (100 mg, 0.23 mmol), (2-mefhylpyridin-3- yl)boronic acid (47 mg, 0.34 mmol), cesium carbonate (148 mg, 0.45 mmol) and Pd(dppf)Cl2 (20 mg, 0.03 mmol) in dioxane/H20 (5: 1, 3 mL) was heated at 85 C under microwave conditions for 0.5 h, at which time LCMS indicated the reaction had gone to completion. The solvent was evaporated under reduced pressure and the crude product was purified by reverse phase chromatography (acetonitrile 30-50% / 0.1% NH4OH in water) to give the title compound (24 mg, 21% yield) as a yellow solid. 1H NMR (400 MHz, OMSO-d6): delta 1 1.95 (s, 1 H), 8.58 (s, 1 H), 8.51-8.50 (m, 1 H), 7.81-7.78 (m, 1 H), 7.34-7.31 (m, 1 H), 7.26 (s, 1 H), 7.03 (s, 1 H), 6.02-5.93 (m, 2 H), 5.17-5.14 (m, 1 H), 5.06-5.02 (m, 1 H), 4.62-4.61 (m, 4 H), 4.35-4.32 (s, 1 H), 3.93-3.89 (m, 2 H), 2.90 (s, 3 H), 2.79 (s, 3 H), 2.32 (s, 3 H), 1.76-1.72 (m, 4 H). LCMS M/Z (M+H) 498.

Reference： [1]Patent: WO2016/77375,2016,A1 .Location in patent: Page/Page column 178

40
8-bromo-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine [ No CAS ]
[ 899436-71-6 ]
[ 875-96-7 ]

Yield	Reaction Conditions	Operation in experiment
46%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; acetonitrile; at 110℃; for 3h;Inert atmosphere;	(0522) To a mixture of A1 (40 mg, 0.110 mmol) in 1,4-dioxane (3 mL), MeCN (0.30 mL) and water (0.30 mL) was added <strong>[899436-71-6](2-methylpyridin-3-yl)boronic acid</strong> (30.1 mg, 0.220 mmol), potassium carbonate (45.5 mg, 0.330 mmol) and Pd(Ph3P)4 (12.69 mg, 10.98 mumol). The resulting mixture was stirred under N2 at 110 C. for 3 h, cooled to rt, and evaporated under vacuum. The residue was purified on flash chromatography (DCM: MeOH=10:1) to afford Example 2 as a white solid (20 mg, 46.0%).

Reference： [1]Patent: US2016/176882,2016,A1 .Location in patent: Paragraph 0521; 0522

41
4-bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-[4-(2H-tetrazol-5-yl)phenyl]-L-phenylalaninamide [ No CAS ]
[ 76-05-1 ]
[ 899436-71-6 ]
N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-(2-methylpyridin-3-yl)-N-[4-(2H-tetrazol-5-yl)phenyl]-L-phenylalaninamide trifluoroacetate [ No CAS ]
C₂₉H₃₅N₉O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 37A N-alpha-[(trans-4-[(tert-Butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-(2-methylpyridin-3-yl)-N-[4-(2H-tetrazol-5-yl)phenyl]-L-phenylalaninamide trifluoroacetate (0543) (0544) 100 mg (0.16 mmol) of 4-bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-[4-(2H-tetrazol-5-yl)phenyl]-L-phenylalaninamide and 18.4 mg (0.02 mmol) of tetrakis(triphenylphosphine)palladium(0) were taken up in 1.5 ml of 1,2-dimethoxyethane and stirred at RT for 10 min. A solution of 66 mg (0.48 mmol) of <strong>[899436-71-6](2-methylpyridin-3-yl)boronic acid</strong> in 0.50 ml of ethanol was added dropwise to the reaction mixture. After the addition of 1.2 ml of 2N aqueous sodium carbonate solution, the mixture was stirred under reflux for 3 h. 1N aqueous hydrochloric acid was added to the reaction mixture, the salts were filtered off and the filtrate was separated by preparative HPLC (mobile phase: acetonitrile/water gradient, 0.1% trifluoroacetic acid). This gave 63 mg of a mixture of the title compound and the corresponding deprotected amine, which was used directly in the next stage. (0545) LC-MS (Method 1): Rt=0.77 min; MS (ESIneg): m/z=637 [M-H-TFA]-.

Reference： [1]Patent: US2016/280699,2016,A1 .Location in patent: Paragraph 0543; 0544; 0545

42
4-bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide [ No CAS ]
[ 76-05-1 ]
[ 899436-71-6 ]
N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-(2-methylpyridin-3-yl)-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide trifluoroacetate [ No CAS ]
C₃₀H₃₄N₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 51A N-alpha-[(trans-4-[(tert-Butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-(2-methylpyridin-3-yl)-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide trifluoroacetate Under argon, 100 mg (0.16 mmol) of 4-bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide and 27 mg (0.03 mmol) of 1,1'-bis(diphenylphosphine)ferrocenepalladium(II) chloride were taken up in 1.4 ml of 1,2-dimethoxyethane and stirred at RT for a few minutes. A solution of 67 mg (0.49 mmol) of <strong>[899436-71-6]2-methylpyridine-3-boronic acid</strong> in 0.54 ml of ethanol was added dropwise to the reaction mixture and stirred at RT for a few minutes. After the addition of 1.2 ml of 2N aqueous sodium carbonate solution, the mixture was stirred at RT for 5 min and irradiated in the microwave at 120 C. for 1 h. A little methanol was added and the reaction mixture filtered through kieselguhr and a Millipore syringe filter and separated by preparative HPLC (mobile phase: acetonitrile/water gradient, 0.1% trifluoroacetic acid). This gave 55 mg of a mixture of the title compound and the partially deprotected title compound, which was used directly in the next stage. LC-MS (Method 1): Rt=0.70 min; MS (ESIneg): m/z=625 [M-H-TFA]-.

Reference： [1]Patent: US2016/280699,2016,A1 .Location in patent: Paragraph 0585; 0586; 0587

43
6-fluoro-5-iodo-[1,2,4]triazolo[1,5-a]pyridine [ No CAS ]
[ 899436-71-6 ]
6-fluoro-5-(2-methylpyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;	Step 1 : A suspension of 6-fluoro-5-iodo-[1,2,4]triazolo[1,5-a]pyridine (Intermediate 18, 0.2 g, 0.760 mmol), <strong>[899436-71-6](2-methylpyridin-3-yl)boronic acid</strong> (CAS 899436-71-6, 0.125 g, 0.913 mmol), PdCl2(dppf) (0.056 g, 0.076 mmol) and Na2C03 (0.161 g, 1.521 mmol) in dioxane (2 mL) and water (0.5 mL) was heated to 100 C for 0.5 h. The reaction was partitioned between EtOAc and water. The organic phase was collected, washed with brine, dried (phase separator) and concentrated in vacuo. The resulting residue was purified by flash chromatography (0-100% EtOAc in petrol on basic silica) to afford 6-fluoro-5-(2-methylpyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridine. MS ES+: 229

Reference： [1]Patent: WO2016/148306,2016,A1 .Location in patent: Page/Page column 207

44
[ 881678-18-8 ]
[ 899436-71-6 ]
[ 928325-22-8 ]

Yield	Reaction Conditions	Operation in experiment
22%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 105℃; for 3h;	General procedure: A suspension of compound 19a (455 mg, 1.02 mmol), (2-fluoropyridin-3-yl)boronic acid (173 mg, 1.23 mmol), tetrakis(triphenylphosphine)palladium (178 mg, 0.154 mmol) and Na2CO3 (258 mg, 2.43 mmol) in DME (10 mL) and water (5 mL) was stirred at 105C for 3 h. After coolingto room temperature, the reaction mixture was diluted with H2O, and extracted with EtOAc. The extract was washedwith a solution of NaHCO3, H2O and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography(n-hexane/EtOAc = 3/1) to obtain

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3298 - 3314

45
ethyl 2-(1-(4-((3-bromobenzo[b]thiophen-5-yl)methoxy)phenyl)-3-oxocyclobutyl)acetate [ No CAS ]
[ 899436-71-6 ]
ethyl 2-(1-(4-((3-(2-methylpyridin-3-yl)benzo[b]thiophen-5-yl)methoxy)phenyl)-3-oxocyclobutyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In N,N-dimethyl-formamide; at 60℃;Inert atmosphere;	General Procedure A: (0434) A mixture of an arylbromide or aryliodide (1 mmol), an arylboronic acid, aryldioxaborolane or bis(pinacolato)diboron (1.5 mmol), a palladium catalyst (0.1 mmol) and K2CO3 (2-3 mmol) was placed in a reaction vessel which was then thoroughly purged with argon. Dioxane (3 mL) and water (1.5 mL) were added, and the mixture was stirred at 80-95 C. for 1 to 3 h. After cooling to rt, the mixture was poured into EtOAc/H2O (1:1, 10 mL) and the aqueous layer was extracted with EtOAc (5 mL×2). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. Purification of the resultant residue by silica gel chromatography (EtOAc/heptanes) afforded the desired biaryl product (A) Ethyl 2-(1-(4-((3-(2-methylpyridin-3-yl)benzo[b]thiophen-5-yl)methoxy)phenyl)-3-oxocyclobutyl)acetate was prepared from ethyl 2-(1-(4-((3-bromobenzo[b]thiophen-5-yl)methoxy)phenyl)-3-oxocyclobutyl)acetate (from Example 32C) and <strong>[899436-71-6](2-methylpyridin-3-yl)boronic acid</strong> following General Procedure A, using PdCl2(dppf).CH2Cl2 as the palladium catalyst and DMF as solvent at a reaction temperature of 60 C. overnight. LC/MS: mass calcd. for C29H27NO4S: 485.59, found: 486.3 [M+H]+.

Reference： [1]Patent: US2017/290800,2017,A1 .Location in patent: Paragraph 0433; 0434; 0648

46
N-(4-(4-amino-7-(1-isobutyrylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl)-5-bromo-1-cyclopropyl-6-methyl-4-oxo-1,4-dihydropyridine-3-carboxamide [ No CAS ]
[ 76-05-1 ]
[ 899436-71-6 ]
N-(4-(4-Amino-7-(1-isobutyrylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl)-1-cyclopropyl-2,2'-dimethyl-4-oxo-1,4-dihydro-[3,3'-bipyridine]-5-carboxamide trifluoroacetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 142. N-(4-(4-Amino-7-(1-isobutyrylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl)-1-cyclopropyl-2,2'-dimethyl-4-oxo-1,4-dihydro-[3,3'-bipyridine]-5-carboxamide To a solution of <strong>[899436-71-6](2-methylpyridin-3-yl)boronic acid</strong> (4.3 mg, 0.032 mmol) and N-(4-(4-amino-7-(1-isobutyrylpiperidin-4-yl)pyrrolo[1,2-f][1,2,4]triazin-5-yl)phenyl)-5-bromo-1-cyclopropyl-6-methyl-4-oxo-1,4-dihydropyridine-3-carboxamide (20.0 mg, 0.032 mmol) (Example 141, step 4) in 1,4-dioxane (2.0 mL) and water (0.2 mL) were added K2CO3 (26.0 mg, 0.188 mmol) and Pd(Ph3P)4 (10.1 mg, 8.7 mumol). The reaction mixture was heated at reflux and stirred for 12 h, cooled to rt, and purified via pH 2 preparative LC/MS (MeCN/water with TFA) to give the product as TFA salt. LCMS calcd for C37H41N8O3 (M+H)+: m/z=645.3. Found: 645.1.

Reference： [1]Patent: US2017/275290,2017,A1 .Location in patent: Paragraph 1406; 1407

47
3-bromobenzo[b]thiophene-5-carbaldehyde [ No CAS ]
[ 899436-71-6 ]
C₁₅H₁₁NOS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 80℃; for 2h;Inert atmosphere;	General procedure: To the mixture of compoundS3(10.0 g, 41.5 mmol), (2-methylphenyl)boronic acid (8.50 g, 62.5 mmol), Pd(dppf)Cl2(1.50 g, 2.05 mmol) and Cs2CO3(34.2 g, 105 mmol) was added 1,4-dioxane (100 mL) and water (25 mL) under nitrogen. The resulting mixture was stirred for 2 h at 80oC in an oil bath. After cooling to rt, the reaction was quenched by H2O (200 mL). The resulting solution was extracted with ethyl acetate (3 x 200 mL), and the organic layers were combined and concentrated under vacuum. The residue was applied onto a silica gel column, eluting with ethyl acetate/petroleum ether (1:50-1:10 v/v). CompoundS4was obtained as a white solid (10.1 g, 87 % yield).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 429 - 436

48
8-bromo-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine [ No CAS ]
[ 899436-71-6 ]
N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8-(2-methylpyridin-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine [ No CAS ]

Reference： [1]Patent: WO2017/219948,2017,A1 .Location in patent: Paragraph 00162

49
(8-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-yl)-(1-ethyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)amine [ No CAS ]
[ 899436-71-6 ]
(1-ethyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-[8-(2-methylpyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl]amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; chloro(2-dicyclohexylphosphino-2?,6?-dimethoxy-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II); In tetrahydrofuran; water; at 120℃; for 16h;Inert atmosphere;	General procedure: To a mixture of chloro triazolopyridine 39b(1 equiv), the respective aryl boronic acid (2 equiv) and K3PO4(2 equiv) in THF/water mixture (0.1 M, v/v 10:1) was addedchloro-(2-dicyclohexylphosphino-20,60-dimethoxy-1,10-biphenyl)-[2-(20amino-1,10-biphenyl)]palladium(II) (0.1 equiv) under argonatmosphere. The reaction mixture was degassed, put under argonatmosphere again and heated at 120 C for 16 h. After cooling toRT the mixture was filtered and purified by preparative reversephase HPLC to give the products.

Reference： [1]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 3227 - 3241

50
[ 899436-71-6 ]
tert-butyl 2-(2-methylpyridin-3-yl)piperidine-1-carboxylate [ No CAS ]

Reference： [1]British Journal of Pharmacology,2018,vol. 175,p. 3470 - 3485

51
[ 899436-71-6 ]
C₁₁H₁₆N₂*ClH [ No CAS ]

Reference： [1]British Journal of Pharmacology,2018,vol. 175,p. 3470 - 3485

52
[ 899436-71-6 ]
N-(4-(2-(2-methylpyridin-3-yl)piperidin-1-ylsulfonyl)phenyl)benzo[d][1,3]dioxole-5-carboxamide [ No CAS ]

Reference： [1]British Journal of Pharmacology,2018,vol. 175,p. 3470 - 3485

53
[ 1372716-04-5 ]
[ 899436-71-6 ]
tert-butyl 6-(2-methylpyridin-3-yl)-3,4-dihydropyridine-1(2H)-carboxylate [ No CAS ]

Reference： [1]British Journal of Pharmacology,2018,vol. 175,p. 3470 - 3485

54
1-(3-iodophenyl)-4-(4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl)pyrrolidin-2-one [ No CAS ]
[ 899436-71-6 ]
1-(3-(2-methylpyridin-3-yl)phenyl)-4-(4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl)pyrrolidin-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 9205 - 9217

55
1-(3-bromo-4-fluorophenyl)-4-(4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl)pyrrolidin-2-one [ No CAS ]
[ 899436-71-6 ]
1-(4-fluoro-3-(2-methylpyridin-3-yl)phenyl)-4-(4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl)pyrrolidin-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 9205 - 9217

56
1-(3-fluoro-5-iodophenyl)-4-[4-(thiazole-2-carbonyl)piperazin-1-yl]pyrrolidin-2-one [ No CAS ]
[ 899436-71-6 ]
1-(3-fluoro-5-(2-methylpyridin-3-yl)phenyl)-4-(4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl)pyrrolidin-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 9205 - 9217

57
1-(3-bromo-5-fluorophenyl)-4-(4-(pyrimidin-2-yl)piperazin-1-yl)pyrrolidin-2-one [ No CAS ]
[ 899436-71-6 ]
1-(3-fluoro-5-(2-methylpyridin-3-yl)phenyl)-4-(4-(pyrimidin-2-yl)piperazin-1-yl)pyrrolidin-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 9205 - 9217

58
[ 1581780-53-1 ]
[ 899436-71-6 ]
[ 1581780-55-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 406 - 412

59
[ 1564238-41-0 ]
[ 899436-71-6 ]
[ 1564227-32-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 406 - 412

60
9-bromo-5-methyl-5,6-dihydrospiro[benzo[f]pyrrolo[1,2-a][1,4]diazepine-6,1'-cyclobutan]-4-one [ No CAS ]
[ 899436-71-6 ]
9-(2-methylpyridin-3-yl)-5-methyl-5,6-dihydrospiro[benzo[f]pyrrolo[1,2-a][1,4]diazepine-6,1'-cyclobutan]-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; at 100℃; for 2h;Inert atmosphere;	General procedure: Under inert atmosphere, a mixture of halide F, Fl or F2 (1 0 equivj, boronic acid derivative G (1.5 equiv.) and PdCI2(dppf).CH2CI2 (010 equiv.) in a mixture of DMF or DMA (0.10 moLL1) and aqueous K2C03 (1.2 moW1) was heated at 110C for 16 hours. After cooling, the reaction mixture was hydrolysed and extracted twice with EtOAc, The organic layers were combined, washed with brine, dried over MgSO4, concentrated and purified to afford the product

Reference： [1]Patent: WO2018/206820,2018,A1 .Location in patent: Page/Page column 200; 212; 213

61
10-chloro-6-methyl-6,7-dihydrospiro[dibenzo[c,e]azepine-7,1'-cyclopropan]-5-one [ No CAS ]
[ 899436-71-6 ]
10-(2-methylpyridin-3-yl)-6-methyl-6,7-dihydrospiro[dibenzo[c,e]azepine-7,1'-cyclopropan]-5-one hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Exampe 21 was prepared according to general procedure lV(i), starting from example 19 and heating at 100 C for 1 hour. Purification by column chromatography on silica gel (using 20%to 100% EtOAc in cyclohexane as eluent) afforded the product as a white solid in 67% yield.Saft formation was performed according to method V(). 1HNMR (400 MHz, DMSOD6): 8.75(dd, J 5,5, 1.3 Hz, 1 H, Ar); 8.40 (d, J 7,9 Hz, 1 H, Ar); 7.85 (dd, J 7,9, 5.5 Hz, I H, Ar); 7.82 (d, J1.6 Hz, I H, Ar); 7.77 (dd, J 7.7, 1.3 Hz, 1 H, Ar); 7.71 (dd, J 7.7, 1.0 Hz, 1 H, Ar); 7.667.61 (m,2H, Ar); 7,577.53 (m, 2H, Ar); 2.99 (s, 3H, CH3); 2.70 (s, 3H, CH3); 1.47 (m, 2H, cyclopropyl);0.87 (m, 1H, cyclopropyl); 0.39 (m, IH, cyclopropyl). MIZ (M+H) = 340.9. MP> 250 C

Reference： [1]Patent: WO2018/206820,2018,A1 .Location in patent: Page/Page column 200; 216

62
10-bromo-3-chloro-6-methyl-6,7-dihydrospiro[dibenzo[c,e]azepine-7,1'-cyclopropan]-5-one [ No CAS ]
[ 899436-71-6 ]
3-chloro-10-(2-methylpyridin-3-yl)-6-methyl-6,7-dihydrospiro[dibenzo[c,e]azepine-7,1'-cyclopropan]-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; at 100℃; for 1h;Inert atmosphere;	General procedure: Under inert atmosphere, a mixture of halide F, Fl or F2 (1 0 equivj, boronic acid derivative G (1.5 equiv.) and PdCI2(dppf).CH2CI2 (010 equiv.) in a mixture of DMF or DMA (0.10 moLL1) and aqueous K2C03 (1.2 moW1) was heated at 110C for 16 hours. After cooling, the reaction mixture was hydrolysed and extracted twice with EtOAc, The organic layers were combined, washed with brine, dried over MgSO4, concentrated and purified to afford the product.

Reference： [1]Patent: WO2018/206820,2018,A1 .Location in patent: Page/Page column 200

63
10-bromo-3-chloro-6-methyl-6,7-dihydrospiro[dibenzo[c,e]azepine-7,1'-cyclopropan]-5-one [ No CAS ]
[ 899436-71-6 ]
3-(2-methyl-2H-pyrazol-3-yl)-10-(2-methylpyridin-3-yl)-6-methyl-6,7-dihydrospiro[dibenzo[c,e]azepine-7,1'-cyclopropan]-5-one [ No CAS ]

Reference： [1]Patent: WO2018/206820,2018,A1

64
[ 899436-71-6 ]
2-(2-(2-methylpyridin-3-yl)phenyl)ethanamine [ No CAS ]

Reference： [1]Patent: WO2019/43139,2019,A1

65
[ 899436-71-6 ]
N-(2-(2-methylpyridin-3-yl)phenethyl)-2H-benzo[e][1,2,4]thiadiazine-3-carboxamide 1,1-dioxide [ No CAS ]

Reference： [1]Patent: WO2019/43139,2019,A1

66
[ 19472-74-3 ]
[ 899436-71-6 ]
2-(2-(2-methylpyridin-3-yl)phenyl)acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With tetrakis(triphenylphosphine) palladium(0); water; potassium carbonate; In isopropyl alcohol; at 80℃; for 5h;Inert atmosphere;	(2-Methylpyridin-3-yl)boronic acid (550 mg, 3.2 mmol), 2-(2-bromophenyl)acetonitrile (597 mg, 3.05 mmol), Pd(PPh3)4 (176 mg, 0.15 mmol) and K2C03 (176 mg, 0.15 mmol) were dissolved in /'PrOH (5 mL) and water (2 mL) and the mixture was heated at 80 C under N2 for 5h. The mixture was filtered and the solid was washed with DCM (20 mL). The filtrate was washed with brine, dried over sodium sulfate and concentrated. Column chromatography (DCM/MeOH = 100:0 - 20:1) gave the product (300 mg, 45% yield) as a yellow solid. LCMS (ES-API): Rt 0.44 min; m/z 209.1 [M+H]+.

Reference： [1]Patent: WO2019/43139,2019,A1 .Location in patent: Page/Page column 109

67
(1S,4S)-tert-butyl 5-(5-bromo-2-(2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamido)phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate [ No CAS ]
[ 76-05-1 ]
[ 899436-71-6 ]
(x)C₂HF₃O₂*C₂₉H₂₇FN₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A mixture of /e/V-butyl (lri',4ri)-5-(5-bromo-2-(2-(2-fluoro-6- methoxyphenyl)pyrimidine-4-carboxamido)phenyl)-2,5-diazabicyclo[2.2. l]heptane-2- carboxylate (10 mg, 0.017 mmol), <strong>[899436-71-6](2-methylpyridin-3-yl)boronic acid</strong> (4.6 mg, 0.033 mmol), XPhosPd G2 (1.3 mg, 1.6 pmol) and potassium phosphate, tribasic (6.7 mg, 0.032 mmol) was combined with l,4-dioxane (lmL) and water (O. lmL). The reaction flask was evacuated, back filled with nitrogen, then stirred at 80 C for 1 h. The reaction mixture was cooled to room temperature, the solvents were evaporated in vacuo and TFA (1 mL) was added. The reaction mixture was stirred at room temperature for 10 min, then diluted with CFbCN and water and purified with prep-LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% TFA, at flow rate of 60 mL/min) to provide the TFA salt of the title compound. LCMS calculated for C29H28FN6O2 (M+H)+: m/z = 511.2; Found: 511.2. NMR (600 MHz, DMSO-rie) d 10.54 - 10.46 (s, 1H), 9.33 - 9.18 (d, J= 5.0 Hz, 1H), 9.06 - 8.91 (s, 1H), 8.80 - 8.74 (s, 1H), 8.67 - 8.63 (dd, J= 5.2, 1.8 Hz, 1H), 8.20 - 8.14 (d, J= 5.0 Hz, 1H), 8.14 - 8.09 (d, J = 8.2 Hz, 1H), 8.09 - 7.98 (d, J= 8.1 Hz, 1H), 7.70 - 7.61 (m, 1H), 7.61 - 7.55 (td, J= 8.4, 6.8 Hz, 1H), 7.31 - 7.27 (d, J= 1.9 Hz, 1H), 7.21 - 7.15 (dd, J= 8.2, 1.8 Hz, 1H), 7.12 - 7.06 (d , J= 8.5 Hz, 1H), 7.06 - 6.96 (t, J= 8.8 Hz, 1H), 4.39 - 4.30 (s, 1H), 4.28 - 4.17 (s, 1H), 3.84 - 3.71 (s, 3H), 3.62 - 3.52 (m, 1H), 3.39 - 3.34 (d, J = 11.2 Hz, 1H), 3.34 - 3.28 (m, 1H), 3.15 - 3.04 (m, 1H), 2.63 - 2.58 (s, 3H), 1.97 - 1.90 (dd, J= 10.8, 2.5 Hz, 1H), 1.84 - 1.67 (m, 1H).

Reference： [1]Patent: WO2019/164846,2019,A1 .Location in patent: Page/Page column 121-122

68
8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5-amine [ No CAS ]
[ 899436-71-6 ]
N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8-(2-methylpyridin-3-yl)imidazo[1,5-c]pyrimidin-5-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In 1,4-dioxane; water at 90℃; Inert atmosphere;

Reference： [1]Rej, Rohan Kalyan; Wang, Changwei; Lu, Jianfeng; Wang, Mi; Petrunak, Elyse; Zawacki, Kaitlin P.; McEachern, Donna; Fernandez-Salas, Ester; Yang, Chao-Yie; Wang, Lu; Li, Ruiting; Chinnaswamy, Krishnapriya; Wen, Bo; Sun, Duxin; Stuckey, Jeanne; Zhou, Yunlong; Chen, Jianyong; Tang, Guozhi; Wang, Shaomeng [Journal of Medicinal Chemistry, 2020, vol. 63, # 13, p. 7252 - 7267]

69
9-bromo-4-((4,6-dimethylpyridin-2-yl)methyl)-7-((2-methyl-1H-imidazol-1-yl)methyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one [ No CAS ]
[ 899436-71-6 ]
4-((4,6-dimethylpyridin-2-yl)methyl)-7-((2-methyl-1H-imidazol-1-yl)methyl)-9-(2-methylpyridin-3-yl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate at 100℃; for 7.5h;	44 4-((4,6-Dimethylpyridin-2-yl)methyl)-7-((2-methyl-l/ -imidazol-l-yl)methyl)-9-(2- methylpyridin-3-yl)-3,4-dihydrobenzo[][l,4]oxazepin-5(2Ef)-one [00265] The title compound (3.0 mg, 9% yield) was prepared from the procedure described in Example 3, Step F using 9-bromo-4-((4,6-dimethylpyridin-2-yl)methyl)-7-((2-methyl-liT- imidazol-l-yl)methyl)-3,4-dihydrobenzo[/][l,4]oxazepin-5(2F/)-one (30.0 mg, 0.07 mmol, 1.0 equiv.), (2-methylpyridin-3-yl)boronic acid (22.6 mg, 0.16 mmol, 2.5 equiv.), K2CO3 (36.4 mg, 0.26 mmol, 4.0 equiv.), and PdCl2(dppf) (2.4 mg, 0.01 mmol, 0.05 equiv.). The reaction mixture was stirred at 100 °C for 7.5 h. LCMS: RT = 0.150 min, MS (ES) 468.6 [M+H]+.

Reference： [1]Current Patent Assignee: VANDERBILT UNIVERSITY - WO2020/247679, 2020, A1 Location in patent: Paragraph 00265

70
3-bromo-7-oxocyclohepta-1,3,5-trien-1-yl tert-butyl carbonate [ No CAS ]
[ 899436-71-6 ]
C₁₈H₁₉NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99 mg	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; caesium carbonate In 1,4-dioxane; water at 120℃; for 0.5h; Inert atmosphere;	53.1 Step 1: To a mixture of building block BB6 (150 mg, 498 umol, 1 eq) and (2-methyl-3- pyridyl)boronic acid (81 mg, 597 umol, 1.2 eq) in dioxane (2.1 mL) and H2O (0.1 mL) was added Pd(dppf)Ch.CH2Cl2 (81 mg, 99.6 umol, 0.2 eq) and CS2CO3 (324 mg, 996 umol, 2 eq) at 25°C under N2. The mixture was degassed and recharged with nitrogen, repeated three times. The resulting mixture was heated and stirred at 120°C for 30 minutes. TLC (Petroleum ether : Ethyl acetate = 1:1) showed the starting material was consumed completely and one major new spot was detected. The mixture was filtered, and the filter cake was washed with ethyl acetate (10 mL x 2). The combined filtrates were washed with brine (10 mL), dried over Na2SC>4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (S1O2, Ethyl acetate, Rf = 0.4) to give 53a (99 mg, 63.4%) as a yellow oil.

Reference： [1]Current Patent Assignee: AMBYS MEDICINES - WO2021/76945, 2021, A1 Location in patent: Page/Page column 101; 102

71
tert-butyl (2S,4S)-4-(7-bromo-4,8-dichloro-6-fluoro-1H-imidazo[4,5-c]quinolin-1-yl)-2-(cyanomethyl)piperidine-1-carboxylate [ No CAS ]
[ 899436-71-6 ]
tert-butyl (2S,4S)-4-(7-bromo-8-chloro-6-fluoro-4-(2-methylpyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-(cyanomethyl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,4-dioxane; water Sealed tube; Inert atmosphere;

Reference： [1]Current Patent Assignee: INCYTE CORP - WO2021/142252, 2021, A1 Location in patent: Page/Page column 313; 314

72
5-(4-bromophenyl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N-methyl-1,3,4-oxadiazol-2-amine [ No CAS ]
[ 899436-71-6 ]
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N-methyl-5-(4-(2-methylpyridin-3-yl)phenyl)-1,3,4-oxadiazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With C₃₃H₄₈ClP*C₁₂H₁₀NPd⁽²⁺⁾; potassium carbonate In 1,4-dioxane; water at 80℃; for 2h;

Reference： [1]Boyd, Scott; Brown, Martin R.; Coen, Muireann; Collingwood, Olga; Davies, Nichola L.; Doherty, Ann; Fairley, Gary; Goldberg, Kristin; Hardaker, Elizabeth; He, Guang; Hennessy, Edward J.; Hodgson, George; Hopcroft, Philip; Jackson, Anne; Jiang, Xiefeng; Karmokar, Ankur; Lainé, Anne-Laure; Lindsay, Nicola; Mao, Yumeng; Markandu, Roshini; McCoull, William; McLean, Neville; McMurray, Lindsay; Mooney, Lorraine; Musgrove, Helen; Nissink, J. Willem M.; Pflug, Alexander; Rawlins, Philip B.; Reddy, Venkatesh Pilla; Rivers, Emma; Schimpl, Marianne; Smith, Graham F.; Smith, Paul D.; Tentarelli, Sharon; Travers, Jon; Troup, Robert I.; Walton, Josephine; Wang, Cheng; Wilkinson, Stephen; Williamson, Beth; Winter-Holt, Jon; Yang, Dejian; Zheng, Yuting; Zhu, Qianxiu [Journal of Medicinal Chemistry, 2021, vol. 64, # 18, p. 13524 - 13539]

73
[ 352684-69-6 ]
[ 899436-71-6 ]
(1S,2S)-2-fluoro-N-(6-(2-methylpyridin-3-yl)benzo[d]thiazol-2-yl)cyclopropane-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 120℃; for 8h; Inert atmosphere;

Reference： [1]Kwon, Seung-Hwan; Kim, Sangjune; Park, A Yeong; Lee, Saebom; Gadhe, Changdev Gorakshnath; Seo, Bo Am; Park, Jong-Sung; Jo, Suyeon; Oh, Yumin; Kweon, Sin Ho; Ma, Shi-Xun; Kim, Wonjoong R.; Kim, Misoon; Kim, Hyeongjun; Kim, Jae Eun; Lee, Seulki; Lee, Jinhwa; Ko, Han Seok [Journal of Medicinal Chemistry, 2021, vol. 64, # 20, p. 15091 - 15110]

74
(2R)-2-[2-(4-bromophenyl)-3-cyano-1,7-naphthyridin-4-yl]-amino}butanamide [ No CAS ]
[ 899436-71-6 ]
(2R)-2-({3-cyano-2-[4-(2-methylpyridin-3-yl)phenyl]-1,7-naphthyridin-4-yl}amino)butanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With potassium dihydrogenphosphate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) In tetrahydrofuran; water at 20℃; for 16h;

Reference： [1]Wortmann, Lars; Bräuer, Nico; Holton, Simon J.; Irlbacher, Horst; Weiske, Jörg; Lechner, Christian; Meier, Robin; Karén, Jakob; Siöberg, Catrine Berthold; Pütter, Vera; Christ, Clara D.; Ter Laak, Antonius; Lienau, Philip; Lesche, Ralf; Nicke, Barbara; Cheung, Shing-Hu; Bauser, Marcus; Haegebarth, Andrea; Von Nussbaum, Franz; Mumberg, Dominik; Lemos, Clara [Journal of Medicinal Chemistry, 2021, vol. 64, # 21, p. 15883 - 15911]

75
[ 899436-71-6 ]
4-(2-methylpyridin-3-yl)thiazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium t-butanolate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane; water / 24 h / 100 °C 2: hydrogenchloride / dichloromethane; 1,4-dioxane / 27 h / 20 - 40 °C

Reference： [1]Current Patent Assignee: ANIMA BIOTECH - WO2021/252555, 2021, A1

76
N-(4-bromothiazol-2-yl)-4-morpholinobenzamide [ No CAS ]
[ 899436-71-6 ]
N-[4-(2-methyl-3-pyridyl)thiazol-2-yl]-4-morpholino-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); caesium carbonate In 1,4-dioxane; water at 120℃; for 1h; Microwave irradiation;	1 To a degassed solution of /V-(4-bromothiazol-2-yl)-4-morpholinobenzamide (120 mg, 0.326 mmol) in 1,4-dioxane (4 mL) and water (1 mL) was added at room temperature (2-methylpyridin-3-yl) boronic acid (89 mg, 0.652 mmol), bw(di-terf-butyl(4- dimethylaminophenyl)phosphine)dichloropalladium(II) (23 mg, 0.033 mmol) and cesium carbonate (319 mg, 0.978 mmol). The reaction was heated in a microwave at 120°C for 1 hour and cooled to room temperature. The reaction mixture was diluted with ethyl acetate (20 mL) and then filtered through Celite. The filtrate and combined washings were collected. The solvent was evaporated to give an orange oil, which was purified by column chromatography on silica gel (0-75% ethyl acetate in cyclohexane) to afford a yellow solid. Further purification by preparative SFC chromatography afforded /V-[4-(2-methyl-3- pyridyl)thiazol-2-yl]-4-morpholino-benzamide as a white solid. Yield 38 mg (31%). NMR (400 MHz, DMSO) d 12.45 (br s, 1H), 8.46 (dd, J=1.8, 4.8 Hz, 1H), 8.07 (d, J=9.2 Hz, 2H), 8.01 (dd, J=1.8, 7.8 Hz, 1H), 7.43 (s, 1H), 7.33 (dd, J=4.8, 7.8 Hz, 1H), 7.05 (d, J=9.2 Hz, 2H), 3.78-3.74 (m, 4H), 3.31-3.29 (m, 4H), 2.68 (s, 3H). m/z: [ESI+] 381 (M+H)+, (C20H20N4O2S).
31%	With bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); caesium carbonate In 1,4-dioxane; water at 120℃; for 1h; Microwave irradiation;	1 To a degassed solution of /V-(4-bromothiazol-2-yl)-4-morpholinobenzamide (120 mg, 0.326 mmol) in 1,4-dioxane (4 mL) and water (1 mL) was added at room temperature (2-methylpyridin-3-yl) boronic acid (89 mg, 0.652 mmol), bw(di-terf-butyl(4- dimethylaminophenyl)phosphine)dichloropalladium(II) (23 mg, 0.033 mmol) and cesium carbonate (319 mg, 0.978 mmol). The reaction was heated in a microwave at 120°C for 1 hour and cooled to room temperature. The reaction mixture was diluted with ethyl acetate (20 mL) and then filtered through Celite. The filtrate and combined washings were collected. The solvent was evaporated to give an orange oil, which was purified by column chromatography on silica gel (0-75% ethyl acetate in cyclohexane) to afford a yellow solid. Further purification by preparative SFC chromatography afforded /V-[4-(2-methyl-3- pyridyl)thiazol-2-yl]-4-morpholino-benzamide as a white solid. Yield 38 mg (31%). NMR (400 MHz, DMSO) d 12.45 (br s, 1H), 8.46 (dd, J=1.8, 4.8 Hz, 1H), 8.07 (d, J=9.2 Hz, 2H), 8.01 (dd, J=1.8, 7.8 Hz, 1H), 7.43 (s, 1H), 7.33 (dd, J=4.8, 7.8 Hz, 1H), 7.05 (d, J=9.2 Hz, 2H), 3.78-3.74 (m, 4H), 3.31-3.29 (m, 4H), 2.68 (s, 3H). m/z: [ESI+] 381 (M+H)+, (C20H20N4O2S).

Reference： [1]Current Patent Assignee: ANIMA BIOTECH - WO2021/252555, 2021, A1 Location in patent: Paragraph 00461
[2]Current Patent Assignee: ANIMA BIOTECH - WO2021/252555, 2021, A1 Location in patent: Paragraph 00461

77
[ 944804-88-0 ]
[ 899436-71-6 ]
tert-butyl (4-(2-methylpyridin-3-yl)thiazol-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In 1,4-dioxane; water at 100℃; for 24h;	1 To a degassed solution of teri-butyl (4-bromothiazol-2-yl)carbamate ( 1.50 g, 5.37 mmol) in 1 ,4- 1,4-dioxane (20 mL) and water (5 mL) was added at room temperature sodium carbonate (2.28 g, 21.49 mmol), 2-methylpyridine-3-boronic acid (1.10 g, 8.06 mmol) and [l,l'-bis(diphenylphosphino)- ferrocene]dichloropalladium(II), complex with dichloromethane (439 mg, 0.537 mmol). The reaction was heated at 100°C for 24 hours and then cooled to room temperature. Ethyl acetate (40 mL) was added and the layers were separated. The organic layer was dried (MgSCL), filtered and concentrated by evaporation to give a residue, which was purified by column chromatography on silica gel (0-80% ethyl acetate in cyclohexane) to afford terf-butyl (4-(2-methylpyridin-3-yl)thiazol-2-yl)carbamate as an orange solid. (0492) Yield 682 mg (43%). NMR (400 MHz, DMSO) d 11.62 (s, 1H), 8.48 (dd, J=1.6, 4.7 Hz, 1H), 7.96 (dd, J=1.6, 7.6 Hz, 1H), 7.40 (s, 1H), 7.34 (dd, J=4.7, 7.6 Hz, 1H), 2.66 (s, 3H), 1.56 (s, 9H).
43%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In 1,4-dioxane; water at 100℃; for 24h;	1 To a degassed solution of teri-butyl (4-bromothiazol-2-yl)carbamate ( 1.50 g, 5.37 mmol) in 1 ,4- 1,4-dioxane (20 mL) and water (5 mL) was added at room temperature sodium carbonate (2.28 g, 21.49 mmol), 2-methylpyridine-3-boronic acid (1.10 g, 8.06 mmol) and [l,l'-bis(diphenylphosphino)- ferrocene]dichloropalladium(II), complex with dichloromethane (439 mg, 0.537 mmol). The reaction was heated at 100°C for 24 hours and then cooled to room temperature. Ethyl acetate (40 mL) was added and the layers were separated. The organic layer was dried (MgSCL), filtered and concentrated by evaporation to give a residue, which was purified by column chromatography on silica gel (0-80% ethyl acetate in cyclohexane) to afford terf-butyl (4-(2-methylpyridin-3-yl)thiazol-2-yl)carbamate as an orange solid. (0492) Yield 682 mg (43%). NMR (400 MHz, DMSO) d 11.62 (s, 1H), 8.48 (dd, J=1.6, 4.7 Hz, 1H), 7.96 (dd, J=1.6, 7.6 Hz, 1H), 7.40 (s, 1H), 7.34 (dd, J=4.7, 7.6 Hz, 1H), 2.66 (s, 3H), 1.56 (s, 9H).

Reference： [1]Current Patent Assignee: ANIMA BIOTECH - WO2021/252555, 2021, A1 Location in patent: Paragraph 00303
[2]Current Patent Assignee: ANIMA BIOTECH - WO2021/252555, 2021, A1 Location in patent: Paragraph 00303

78
N-(4-bromothiazol-2-yl)-2-methoxypyrimidine-5-carboxamide [ No CAS ]
[ 899436-71-6 ]
2-methoxy-N-[4-(2-methyl-3-pyridyl)thiazol-2-yl]pyrimidine-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); caesium carbonate In 1,4-dioxane; water at 120℃; for 1h; Microwave irradiation;	1 To a degassed mixture of iV-(4-bromothiazol-2-yl)-2-methoxypyrimidine-5-carboxamide (150 mg, 0.476 mmol) and (2-methylpyridin-3-yl)boronic acid (130 mg, 0.952 mmol) in 1,4-dioxane (4 mL) was added at room temperature /?/i(di-teri-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (34 mg, 0.048 mmol) and a solution of cesium carbonate (465 mg, 1.43 mmol) in water (0.5 mL). The reaction mixture was heated at 120°C in a microwave for 1 hour. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (20 mL) and filtered through Celite. The filtrate was evaporated and the residue purified by column chromatography on silica gel (0-50% ethyl acetate in cyclohexane) to afford 2-methoxy-/V-[4-(2-methyl-3-pyridyl)thiazol-2-yl]pyrimidine-5-carboxamide as an off-white solid. (0874) Yield 67 mg (43%). NMR (400 MHz, DMSO) d 13.03 (br s, 1H), 9.29 (s, 2H), 8.51 (dd, J=1.8, 4.7 Hz, 1H), 8.04 (dd, J=1.8, 7.8 Hz, 1H), 7.57 (s, 1H), 7.38 (dd, J=4.7, 7.8 Hz, 1H), 4.08 (s, 3H), 2.72 (s, 3H). m/z: [ESI+] 328 (M+H)+, (C15H13N5O2S).
43%	With bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); caesium carbonate In 1,4-dioxane; water at 120℃; for 1h; Microwave irradiation;	1 To a degassed mixture of iV-(4-bromothiazol-2-yl)-2-methoxypyrimidine-5-carboxamide (150 mg, 0.476 mmol) and (2-methylpyridin-3-yl)boronic acid (130 mg, 0.952 mmol) in 1,4-dioxane (4 mL) was added at room temperature /?/i(di-teri-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (34 mg, 0.048 mmol) and a solution of cesium carbonate (465 mg, 1.43 mmol) in water (0.5 mL). The reaction mixture was heated at 120°C in a microwave for 1 hour. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (20 mL) and filtered through Celite. The filtrate was evaporated and the residue purified by column chromatography on silica gel (0-50% ethyl acetate in cyclohexane) to afford 2-methoxy-/V-[4-(2-methyl-3-pyridyl)thiazol-2-yl]pyrimidine-5-carboxamide as an off-white solid. (0874) Yield 67 mg (43%). NMR (400 MHz, DMSO) d 13.03 (br s, 1H), 9.29 (s, 2H), 8.51 (dd, J=1.8, 4.7 Hz, 1H), 8.04 (dd, J=1.8, 7.8 Hz, 1H), 7.57 (s, 1H), 7.38 (dd, J=4.7, 7.8 Hz, 1H), 4.08 (s, 3H), 2.72 (s, 3H). m/z: [ESI+] 328 (M+H)+, (C15H13N5O2S).

Reference： [1]Current Patent Assignee: ANIMA BIOTECH - WO2021/252555, 2021, A1 Location in patent: Paragraph 00450
[2]Current Patent Assignee: ANIMA BIOTECH - WO2021/252555, 2021, A1 Location in patent: Paragraph 00450

79
8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine [ No CAS ]
[ 899436-71-6 ]
N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8-(2-methylpyridin-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine hydrochloride salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / 1,4-dioxane; acetonitrile; water monomer / 3 h / 110 °C 2: hydrogenchloride / isopropanol / 17 h / 20 - 50 °C

Reference： [1]Atadja, Peter; Blanz, Joachim; Chen, Zijun; Dillon, Michael P.; Fang, Douglas; Feng, Lijian; Fu, Xingnian; Gao, Zhenting; Gu, Justin; Huang, Ying; Jeay, Sebastien; Kiffe, Michael; Li, En; Li, Ling; Lingel, Andreas; Luo, Fangjun; Luo, Xiao; Mi, Yuan; Mistry, Prakash; Moggs, Jonathan; Oyang, Counde; Pearson, David; Piaia, Alessandro; Pissot-Soldermann, Carole; Qi, Wei; Scheufler, Clemens; Sendzik, Martin; Sun, Yongfeng; Terranova, Remi; Wang, Long; Weiss, Andreas; Yu, Zhengtian; Zeng, Jue; Zhang, Hailong; Zhang, Jeff; Zhang, Jiangwei; Zhang, Lijun; Zhang, Qiong; Zhao, Kehao; Zhao, Mengxi; Dubost, Valérie [Journal of Medicinal Chemistry, 2022, vol. 65, # 7, p. 5317 - 5333]

80
5-bromo-2-(3,5-dimethoxybenzyl)-7-((2-imino-3-methyl-2,3-dihydro-1H-imidazol-1-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one [ No CAS ]
[ 899436-71-6 ]
2-(3,5-dimethoxybenzyl)-7-((2-imino-3-methyl-2,3-dihydro-1H-imidazol-1-yl)methyl)-5-(2-methylpyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; potassium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 80℃; Inert atmosphere;

Reference： [1]Teuscher, Kevin B.; Meyers, Kenneth M.; Wei, Qiangqiang; Mills, Jonathan J.; Tian, Jianhua; Alvarado, Joseph; Sai, Jiqing; Van Meveren, Mayme; South, Taylor M.; Rietz, Tyson A.; Zhao, Bin; Moore, William J.; Stott, Gordon M.; Tansey, William P.; Lee, Taekyu; Fesik, Stephen W. [Journal of Medicinal Chemistry, 2022, vol. 65, # 8, p. 6287 - 6312]

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CAS No. :	899436-71-6	MDL No. :	MFCD07368825
Formula :	C₆H₈BNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	TWKMYNQPIICYNV-UHFFFAOYSA-N
M.W :	136.94	Pubchem ID :	20111647
Synonyms :

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

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P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
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P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
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P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
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P337 + P313	IF eye irritation persists: Get medical advice/attention.
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P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
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

[ CAS No. 899436-71-6 ] {[proInfo.proName]}

Quality Control of [ 899436-71-6 ]

Related Doc. of [ 899436-71-6 ]

Product Details of [ 899436-71-6 ]

Safety of [ 899436-71-6 ]

Application In Synthesis of [ 899436-71-6 ]

[ 899436-71-6 ] Synthesis Path-Upstream 1~2

[ 899436-71-6 ] Synthesis Path-Downstream 1~80

Related Functional Groups of
[ 899436-71-6 ]

Organoboron

Related Parent Nucleus of
[ 899436-71-6 ]

Pyridines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 899436-71-6 ] {[proInfo.proName]}

Quality Control of [ 899436-71-6 ]

Related Doc. of [ 899436-71-6 ]

Product Details of [ 899436-71-6 ]

Safety of [ 899436-71-6 ]

Application In Synthesis of [ 899436-71-6 ]

[ 899436-71-6 ] Synthesis Path-Upstream 1~2

[ 899436-71-6 ] Synthesis Path-Downstream 1~80

Related Functional Groups of [ 899436-71-6 ]

Organoboron

Related Parent Nucleus of [ 899436-71-6 ]

Pyridines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 899436-71-6 ]

Related Parent Nucleus of
[ 899436-71-6 ]