Name: 659742-21-9|(6-Methylpyridin-3-yl)boronic acid|98%
Brand: Ambeed
SKU: A216887
Price: 5.0 USD
Availability: InStock
Rating: 91 (30 reviews)

1
[ 959909-83-2 ]
[ 659742-21-9 ]
[ 959999-60-1 ]

Yield	Reaction Conditions	Operation in experiment
59%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In ISOPROPYLAMIDE; water; at 80℃;	INTERMEDIATE 9Methyl 3-[(1R)-1-(2-chloro-3-hydroxyphenyl)ethyl]ocy}-5-5-(6-methyl-3-pyridinyl)-1H-benzimidazol-1-yl]-2-thiophenecarboxylate To a solution of methyl 5-(5-bromo-1H-benzimidazol-1-yl)-3-[(1R)-1-(2-chloro-3-[(1,1-dimethylethyl)(dimethyl)silyl]oxy}phenyl)ethyl]oxy}-2-thiophenecarboxylate (300 mg, 0.48 mmol) in 4.5 mL of DMA was added 2-picollne-5-boronic acid hydrate (79 mg, 0.58 mmol), 1M Na2CO3 (1.44 ml, 1.44 mmol) and Cl2Pd(dppf) (41 mg, 0.05 mmol), and the reaction was heated to 80 C. The dark reaction was concentrated onto silica gel and purified by flash column chromatography to give the title compound, which was triturated into ether (147 mg, 59%). 1H NMR (400 MHz, d6-DMSO) delta 10.26 (s, 1H), 8.80 (s, 1H), 8.70 (s, 1H), 8.08 (s, 1H), 8.01 (dd, J=8.0 and 2.4 Hz, 1H), 7.68 (m, 2H), 7.34-7.32 (m, 2H), 7.20-7.11 (m, 2H), 6.91 (d, J=8.0 Hz, 1H), 5.93 (m, 1H), 3.70 (s, 3H), 2.49 (s, 3H), 1.60 (d, J=6.0 Hz, 3H).
59%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl acetamide; water; at 80℃;	Intermediate 9: Mefhy. 3-[(1 /^-1-(2-chJoro-3-liyciroxvphbeta?vJ)betathv?oxyKdelta-[5- (6-methvJ-3-pvri?Jinvi)-1Mbenzimidazoi-1-yil-2-thiophenecarboxy.3teTo a solution of methyl 5-{5-bromo-1 Mben2amidazol-1-yl)-3-{(1 lambda)-1-(2-chloro- 3-[{1 , 1 -dimetiiyiethy.)(dimethyi)siiy.Joxy}phenyl)ethyl]oxy}-2- thiophersecarboxylate (300 ing, 0.48 mmo.) in 4.5 mL of DMA was added 2- picoJine-5-boronic acid hydrate (79 mg, 0.58 mmo.), 1 M Na2CO3 (1 lambda4 ml, 1.44 mmol) and CI2Pd(dppf) (41 mg, 0.05 mmo.), and the reaction was heated to 80 0C. The dark reaction was concentrated onto silica gel an purified by flash column chromatography to give the title compound, which was triturated into ether (147 mg, 59%). 1H NMR (400 MHz, dbeta-DMSO) S 10.26 (s5 1H)1 8.80 (s, I H)1 8.70 (S1 1 H), 8.08 (s, 1H)1 8.01 {, J ^B.Q and 2.4 Hz, 1 H)1 7.68 (m, 2H)1 7.34-7.32 (m, 2H)1 7.20-7.11 (m, 2H), 6.91 (d, J -8.0 Hz, 1 H), 5.93 (m, 1H), 3.70 (S1 3H)1 2,49 (S1 3H)1 1.80 (d, 7 - 6.0 Hz1 3H).

Reference： [1]Patent: US2008/300247,2008,A1 .Location in patent: Page/Page column 40
[2]Patent: WO2007/143456,2007,A2 .Location in patent: Page/Page column 93

2
[ 1000793-42-9 ]
[ 659742-21-9 ]
6,6-dimethyl-2-[6-(6-methylpyridin-3-yl)-2,3-dihydrobenzo[1,4]oxazin-4-yl]-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 160℃; for 0.5h;Microwave irradiation;	EXAMPLE 48; 6,6-Dimethyl-2-r6-(6-methylpyridin-3-yl)-2,3-dihydrobenzo?,41oxazin-4-yl1-6,7- dihydroF 1 ,31thiazolor5,4-clpyridin-4(5H)-one <n="190"/>; A stirred solution of Example 39 (0.090 g, 0.23 mmol), 2-methylpyridine-5- boronic acid (0.094 g, 0.69 mmol), Na2CO3 (0.073 g, 0.69 mmol) and tetrakis- (triphenylphosphine)palladium(O) (0.026 g, 0.02 mmol) in THF (3 mL) was heated to 1600C under microwave irradiation for 30 minutes. After cooling to r.t., water (10 mL) was added and the resulting precipitate filtered off, washed with water (3 x 20 mL) and dried in vacuo. The solid was then triturated with EtOAc (3 x 20 mL) and DCM (2 x 20 mL), then concentrated in vacuo to give the title compound (0.027 g, 29%) as an off- white solid. deltaH (CDCl3) 8.71 (IH, d, J 2.3 Hz), 8.22 (IH, d, J 2.1 Hz), 7.75 (IH, dd, J 8.1 and J2.4 Hz), 7.29 (IH, dd, J 7.9 and J2.3 Hz), 7.22 (IH, d, J7.9 Hz), 7.05 (IH, d, J 8.5 Hz), 5.30 (IH, br. s), 4.43-4.37 (2H, m), 4.22-4.16 (2H, m), 2.89 (2H, s), 2.60 (3H, s), 1.40 (6H, s). LCMS (ES+) 407.0 (M+H)+, RT 1.99 minutes (Method 1).

Reference： [1]Patent: WO2008/1076,2008,A1 .Location in patent: Page/Page column 188-189

3
[ 56055-54-0 ]
[ 659742-21-9 ]
[ 1001193-66-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 18h;Heating / reflux;	Example 8: Preparation of 3-chloro-6'-methyl-[2,3']bipyridyl-5-carboxylic acid methyl ester (12)[288] 0.29 of Na CO (0.273 mmol), 0.25 g of 6-methylpyridin-3-ylboronic acid (11)(0.18 mmol) and 0.11 g of Pd(PPh 3 ) 4 were added to 0.4 g of <strong>[56055-54-0]5,6-dichloro-nicotinic acid methyl ester</strong>(ltheta) (0.2 mmol) prepared in Example 7 dissolved in 14 mL of 1,2-dimethoxyethane and 7 mL of distilled water, and refluxed under heating and stirring for 18 hours. The mixture was cooled to room temperature, and concentrated about 50% under reduced pressure. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate, concentrated under reduced pressure. The residue was separated by column chromatography (eluting solvent: chloroform/methanol=10/l) to obtain 0.42 g of 3-chloro-6'-methyl-[2,3'] bipyridyl- 5-carboxylic acid methyl ester (yield 88%).[289] 1U NMR (CDCl ) delta: 9.16 (d, IH), 8.96 (s, IH), 8.40 (d, IH), 8.03 (dd, IH), 7.29 (d,IH), 4.00 (s, 3H), 2.65 (S, 3H)
81%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 18h;Reflux;	Example 8Preparation of 3-chloro-6'-methyl-[2,3']bipyridyl-5-carboxylic acid methyl ester (12)0.29 of Na2CO3 (0.273 mmol), 0.25 g of 6-methylpyridin-3-ylboronic acid (11) (0.18 mmol) and 0.11 g of Pd(PPh3)4 were added to 0.4 g of <strong>[56055-54-0]5,6-dichloro-nicotinic acid methyl ester</strong> (10) (0.2 mmol) prepared in Example 7 dissolved in 14 mL of 1,2-dimethoxyethane and 7 mL of distilled water, and refluxed under heating and stirring for 18 hours. The mixture was cooled to room temperature, and concentrated about 50% under reduced pressure. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate, concentrated under reduced pressure. The residue was separated by column chromatography (eluting solvent: chloroform/methanol=10/1) to obtain 0.42 g of 3-chloro-6'-methyl-[2,3']bipyridyl-5-carboxylic acid methyl ester (yield 88%).1H NMR (CDCl3) delta: 9.16 (d, 1H), 8.96 (s, 1H), 8.40 (d, 1H), 8.03 (dd, 1H), 7.29 (d, 1H), 4.00 (s, 3H), 2.65 (S, 3H)

Reference： [1]Patent: WO2008/7900,2008,A1 .Location in patent: Page/Page column 15; 26
[2]Patent: US2009/209540,2009,A1 .Location in patent: Page/Page column 15; 7

4
[ 1001193-62-9 ]
[ 659742-21-9 ]
[ 1001193-70-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 18h;Heating / reflux;	Example 10: Preparation of 3-chloro-6'-methyl-5-vinyl-2,3'-bipyridine (14)[296] 8.1 g of Na CO (76 mmol), 3.5 g of 6-methylpyridin-3-ylboronic acid (11) (25 mmol), and 0.97 g of Pd(PPh ) were added to 4.9 g of compound (8) (28 mmol) prepared in Example 5 dissolved in 100 mL of 1,2-dimethoxyethane and 100 mL of distilled water, and refluxed under heating and stirring for 18 hours. The mixture was cooled to room temperature, and concentrated about 50% under reduced pressure. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate, concentrated under reduced pressure. The residue was separated by column chromatography (eluting solvent: ethyl acetate/hexane=l/4) to obtain 5.2 g of 3-chloro-6'-methyl-5-vinyl-2,3'-bipyridine (yield 90%).[297] 1U NMR (CDCl ) delta: 8.92 (s, IH), 8.59(s, IH), 7.99 (d, IH), 7.84 (s, IH), 7.28 (s,IH), 6.76-6.66 (m, IH), 5.91 (d, IH), 5.50 (d, IH), 2.64(s, 3H)
90%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 18h;Reflux;	Example 10Preparation of 3-chloro-6'-methyl-5-vinyl-2,3'-bipyridine (14)8.1 g of Na2CO3 (76 mmol), 3.5 g of 6-methylpyridin-3-ylboronic acid (11) (25 mmol), and 0.97 g of Pd(PPh3)4 were added to 4.9 g of compound (8) (28 mmol) prepared in Example 5 dissolved in 100 mL of 1,2-dimethoxyethane and 100 mL of distilled water, and refluxed under heating and stirring for 18 hours. The mixture was cooled to room temperature, and concentrated about 50% under reduced pressure. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate, concentrated under reduced pressure. The residue was separated by column chromatography (eluting solvent: ethyl acetate/hexane=1/4) to obtain 5.2 g of 3-chloro-6'-methyl-5-vinyl-2,3'-bipyridine (yield 90%).1H NMR (CDCl3) delta: 8.92 (s, 1H), 8.59 (s, 1H), 7.99 (d, 1H), 7.84 (s, 1H), 7.28 (s, 1H), 6.76-6.66 (m, 1H), 5.91 (d, 1H), 5.50 (d, 1H), 2.64 (s, 3H)

Reference： [1]Patent: WO2008/7900,2008,A1 .Location in patent: Page/Page column 16; 27
[2]Patent: US2009/209540,2009,A1 .Location in patent: Page/Page column 15-16; 8

5
[ 719310-31-3 ]
[ 659742-21-9 ]
6-(6-methylpyridin-3-yl)-2,3-dihydrobenzo[1,4]oxazine-4-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 120℃; for 1h;Microwave irradiation;	INTERMEDIATE 26; 6-(6-Methylpyridin-3-yl)-2,3-dihvdrobenzo[l,4]oxazine-4-carboxylic acid fert-butyl ester A mixture of Intermediate 25 (220 mg, 0.73 mmol), 2-methylpyridine-5-boronic acid hydrate (100 mg, 0.73 mmol), potassium phosphate (465 mg, 2.19 mmol), tetrakis(triphenylphosphine)palladium(0) (10 mg, catalytic) and water (1 mL) in DME (8 mL) was heated to 1200C under microwave irradiation for 1 h. After cooling to r.t. the <n="34"/>reaction mixture was concentrated in vacuo. The crude material was purified by column chromatography (SiO2, linear gradient elution: 0-50% EtOAc in heptane) to give the title compound as an off-white solid (155 mg, 65%). deltaH (CDCl3) 1.59 (9H, s), 2.60 (3H, s), 3.87-3.97 (2H, m), 4.25-4.35 (2H, m), 6.97 (IH, d, J 8.3 Hz), 7.16-7.24 (2H, m), 7.74 (IH, dd, J 8.1, 2.4 Hz), 8.04 (IH, br s), 8.70 (IH, d, J2.6 Hz).

Reference： [1]Patent: WO2008/44022,2008,A1 .Location in patent: Page/Page column 32-33

6
2-(7-bromo-2,3-dihydrobenzo[1,4]oxazin-4-yl)-5,5-dimethyl-5,6-dihydro-4H-benzothiazol-7-one [ No CAS ]
[ 659742-21-9 ]
5,5-dimethyl-2-[7-(6-methylpyridin-3-yl)-2,3-dihydrobenzo[1,4]oxazin-4-yl]-5,6-dihydro-4H-benzothiazol-7-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 150℃; for 1.33333h;Microwave irradiation;	EXAMPLE 60; 5.5-Dimethyl-2-[7-('6-methylpyridin-3-yl)-2.3-dihvdrobenzorL41oxazin-4-yll-5.6- dihydro-4H-benzothiazol-7-one; Example 2 (90 mg, 0.23 mmol), 2-methylpyridine-5-boronic acid (94 mg, 0.68 mmol), sodium carbonate (74 mg, 0.68 mmol) and tetrakis(triphenylphosphine)- palladium(O) (26 mg, 0.02 mmol) in water (1 mL) and THF (4 mL) were heated to 1500C under microwave irradiation for 30 min. Additional portions of the boronic acid (94 mg, 0.68 mmol) and tetrakis(triphenylphosphine)palladium(0) (26 mg, 0.02 mmol) were added, and heating continued for a further 50 min. After cooling to r.t. the reaction mixture was partitioned between EtOAc (50 mL) and saturated aqueous sodium bicarbonate (50 mL). The organics were washed with brine (50 mL), dried (MgSO4) and concentrated in vacuo. The crude material was purified by prep HPLC to give the title compound as an off-white solid (17 mg, 18%). deltaH (CDCl3) 1.09 (6H, s), 2.37 (2H, s), <n="66"/>2.54 (3H, s), 2.71 (2H, s), 4.12-4.18 (2H, m), 4.29-4.35 (2H, m), 7.08-7.18 (3H, m), 7.69 (IH, dd, J 7.9, 2.3 Hz), 8.00 (IH, d, J 9.0 Hz), 8.65 (IH, s). LCMS (ES+) 406 (M+H)+.

Reference： [1]Patent: WO2008/44022,2008,A1 .Location in patent: Page/Page column 64-65

7
[ 1207382-80-6 ]
[ 659742-21-9 ]
[ 868284-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 95℃;	Next, 6-methylpyridine-3-ylboric acid, tetrakis(triphenylphosphine) palladium and aqueous 2 M sodium carbonate solution were added to a 1,4-dioxane solution of the above compound, and stirred overnight at 95C. The reaction mixture was processed in an ordinary manner to obtain 2-[2-amino-6-(6-methylpyridin-3-yl)pyrimidin-4-yl]phenol as a yellow solid. FAB-MS(M+H)+: 279.

Reference： [1]Patent: EP1736472,2006,A1 .Location in patent: Page/Page column 15

8
C₃₀H₃₆BrN₅O₇S [ No CAS ]
[ 659742-21-9 ]
C₃₆H₄₂N₆O₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 90℃; for 20h;	Example 14: Synthesis of iV-ri7-r5-(4-methvl-3-pvridvl)-6-methoxvisoquinolin-l- yloxy]-13-methyl-2,14-dioxo-3,13,15-triaza-tricyclo[13.3.0.04'6]octadec-7-ene-4- carbonyl] (cyclopropyl)sulfonamide (52).; A solution of 51 (17.3 mg, 0.025 mmol), 6-methylpyridine-3-boronic acid (5.9 mg, 0.028 mmol), tetraf°striphenylphosphine palladium (8.2 mg, 0.005 mmol) and sodium carbonate (5.8 mg, 0.055 mmol) in DMF (2 mL) were warmed to 90C for 20 h. Then, the reaction mixture was cooled down to room temperature and the solvent was evaporated. The residue was purified by HPLC to yield 3.7 mg (21%) of the title product 52 as a white powder, m/z = 703 (M+H)+; 1H-NMR (CDCl3): 10.6 (bs, IH), 8.8 (s, IH), 8.12 (d, J= 9.1 Hz, IH), 7.97 (d, J= 6.3 Hz, IH), 7.9 (d, J= 9.0 Hz, IH), 7.54 (d, J= 6.3 Hz, IH), 7.3 (d, J=9.0 Hz, IH), 7.21 (d, J= 9.1 Hz, IH), 6.68 (br s, IH), 5.87 (br s, IH), 5.74 (dd, J= 17.3 Hz, 8.3 Hz, IH), 5.16 (t, J= 10.4 Hz, IH), 4.74 (dd, J= 9.4 Hz, 7.3 Hz, IH), 4.11-3.98 (m, 4H), 3.69-3.55 (m, 2H), 3.27-3.10 (m, IH), 3.02-2.89 (m, IH), 2.83 (s, 3H), 2.58-2.35 (m, 3H), 2.50 (s, 3H), 2.29-2.13 (m, IH), 2.11-1.92 (m, 2H), 0.75-1.76 (m, 9H).

Reference： [1]Patent: WO2007/14921,2007,A1 .Location in patent: Page/Page column 95

9
[ 111770-91-3 ]
[ 73183-34-3 ]
[ 659742-21-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In acetonitrile; at 160℃; for 0.333333h;Microwave;	The INFLATE (4. 6MMOL) was dissolved in acetonitrile (30MOL) and placed into A 5M . microwave vessel. To the solution was added 1. 5 EQ of bis (PINACOLATO) DIBORON (6. 9MMOL ; 1. 71 G). The mixture was stirred on A magnetic stir plate until dissolution. To the mixture was added KOAC (13. 8MMOL ; 1. 35g) and 98mg of [1,1'-bis (DIPHENYLPHOSPHINO)- FERROCENE] DICHLOROPALLADIUM (II) (0. 03MOI%). The reaction mixture was heated at 160C for 2 X 600s. After completion (monitored by LC-MS), the acetonitrile was evaporated to give a black solid. The solid was dissolved in DMSO, ms and purified by HPLC to give the boronic acid (580mg, 92%; 4. 2MMOL). MS: MH+= 138

Reference： [1]Patent: WO2005/32493,2005,A2 .Location in patent: Page/Page column 40-41

10
[ 2402-77-9 ]
[ 659742-21-9 ]
[ 849757-67-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water;Reflux;	100 g (0.676 mol) of 2,3-dichloropyridine was dissolved in 500 mL of ethanol, and 91.87 g (0.676 mol) of p-tolylboronic acid and 78 g (0.0676 mol) of Pd(PPh3)4 were sequentially added. A solution of 86 g (0.811 mol) of sodium carbonate in 500 mL of distilled water was placed in the reactor, and the mixture was heated to reflux for 4 ~ 6 hours so as to allow it to react. After completion of the reaction, the reaction solution was concentrated under reduced pressure to remove ethanol, and then extracted with ethyl acetate. The extract was treated with magnesium sulfate, filtered, and concentrated under reduced pressure, yielding 3-chloro-2-para-tolylpyridine as represented below in a 87% yield.
85%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; acetonitrile; at 160℃; for 0.0833333h;Microwave;	The above boronic acid (4. 2MMOL) was dissolved in acetonitrile (2MU) and added to A 5M . microwave vessel. To the solution was 6. 9 mmol OF 2, 3-dichloropyridine (L. OLG), 53 mg of tetrakis(triphenylphosphine)palladium (0). After stirring until dissolution, 13. 8mmol of potassium carbonate (1. 90g) was added, followed by LML of water. The mixture was then heated at 160C for 300 seconds. After reaction completion, the solvents were evaporated under vacuum. The target compound was purified by HPLC to give A yellow solid (800mg ; 85%). MS : MH+= 205
80%	With sodium carbonate; In 1,2-dimethoxyethane; water; for 18h;Heating;	Example 136 Preparation of 3-chloro-6?-(6-trifluoromethyl-1H-benzoimidazole-2-yl)-[2,3?]bipyridine (0550) (1) Preparation of 3-chloro-2-(6-methylpyridin-3-yl)pyridine (0551) To a solution of 0.5 g (3.6 mmol) 2,3-dichloropyridine in 20 mL 1,2-dimethoxyethane and 20 mL distilled water were added 2.2 g (21.1 mmol) Na2CO3, 0.41 g (3.0 mmol) 2-methylpyridine-5-boronic acid and 50 mg Pd(PPh3)4, followed by stirring for 18 hours in a heat flux condition. After being cooled to room temperature, the solution was 50% concentrated in a vacuum condition. The aqueous layer was washed with ethyl acetate. Thereafter, the organic layer was dried over magnesium sulfate and vacuum concentrated. The concentrate was separated using column chromatography (developing solvent: ethyl acetate/hexane=1/10) to produce 0.56 g of 3-chloro-2-(6-methylpyridin-3-yl)pyridine (yield 80%). (0552) 1H NMR (CDCl3) delta: 8.91 (d, 1H), 8.63 (dd, 1H), 7.99 (dd, 1H), 7.83 (dd, 1H), 7.49-7.47 (m, 1H), 7.30-7.27 (m, 1H), 2.65 (s, 3H)

Reference： [1]Patent: WO2012/44043,2012,A2 .Location in patent: Page/Page column 20-21
[2]Patent: WO2005/32493,2005,A2 .Location in patent: Page/Page column 41
[3]Patent: US9199965,2015,B2 .Location in patent: Page/Page column 70-71

11
[ 1146977-56-1 ]
[ 659742-21-9 ]
[ 1146977-33-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 24h;	Example 54: 3-ethyl-lambda/,lambda/,4-trimethyl-2-[4-(6-methyl-3-pyridinyl)phenyl]imino}-2,3- dihydro-1,3-thiazole-5-carboxamide hydrochloride; A mixture of 2-[(4-bromophenyl)imino]-3-ethyl-lambda/,lambda/,4-trimethyl-2,3-dihydro-1 ,3-thiazole-5- carboxamide (200 mg, 0.54mmol, Description 27), <strong>[659742-21-9](6-methyl-3-pyridinyl)boronic acid</strong> (223 mg, 1.63mmol), tetrakis(triphenylphosphine)palladium(0) (37.7 mg, 0.03mmol) and sodium carbonate (1 15 mg, 1.09mmol) in 1 ,4-dioxane (12 ml) and water (4 ml) were heated at 100C for 24 hours. The reaction mixture was diluted with ethyl acetate, filtered through kieselguhr to remove catalyst and the filtrate was washed with water, separated organic layer, dried over sodium sulphate. The reaction mixture was concentrated and purified by MDAP to give the crude product. The crude product was partitioned between dichloromethane and aqueous sodium hydrogen carbonate solution, dried over sodium sulphate, filtered and evaporated. The residual material was dissolved in methanol, and treated with 1 M ethereal hydrogen chloride to give the desired product as a white solid (23mg, 9.45%).LC/MS (ES): Found 381 (ES+), retention time 1.43mins. C2iH24N4OS requires 380. 1H-NMR (400MHz, DMSOd6): delta 1.33 (3H, s), 2.31 (3H, s), 3.81 (3H, s), 2.97 (6H, s), 4.29 (2H, m), 7.58 (2H, m), 8.0 (3H, m), 8.83 (1 H, m), 9.12 (1 H, m).

Reference： [1]Patent: WO2009/53448,2009,A1 .Location in patent: Page/Page column 74

12
[ 1146412-23-8 ]
[ 659742-21-9 ]
[ 1146413-21-9 ]

Yield	Reaction Conditions	Operation in experiment
25.3%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 100℃; for 2h;Microwave irradiation;	Example 84^{^-chloro-S-ttrifluoromethylJphenyllcarbony^-i-^-methyl-S-ttheta-methyl-S- pyridinyl)phenyl]-2-piperazinone (E84); A mixture of 1-(3-bromo-2-methylphenyl)-4-[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-piperazinone (250 mg, 0.526 mmol, prepared as described in Example 46), <strong>[659742-21-9](6-methyl-3-pyridinyl)boronic acid</strong> (144 mg, 1.051 mmol) and sodium carbonate (279 mg, 2.63 mmol) in 1 ,2-Dimethoxyethane (DME) (2 ml) and water (2.000 ml) was treated with Pd(Phi3P)4 (364 mg, 0.315 mmol) and the reaction mixture heated in the microwave at 1000C (high absorbtion) for 2 hours. The reaction mixture was diluted with EtOAc (15ml) and NaHCC>3 (sat., aq.) (15ml) and the product was extracted into EtOAc (x2). The combined organic layers were washed with water (15ml), brine (15ml) and then dried over magnesium sulphate. The solvent was evaporated in vacuo to give a dark brown oil. The crude product was purified by column flash-silica gel chromatography eluting with 0 to 100% EtOAc in iso-hexane. No product was found in the fractions collected, so the product was purified again by flash-silica gel chromatography eluting with 0 to 50% methanol in EtOAc. Relevant fractions were combined and solvent evaporated in vacuo to give a brown solution. The mixture was stirred with charcoal and then filter through celite to give a yellow pale product.The product was transformed into an hydrochloric acid salt by adding 2ml of DCM and 1 ml of hydrochloric acid in ether and the solution was left to stir during 1 h at RT. The solvent was evaporated in vacuo, to give a yellow powder. The compound was dried, triturated with ether and then dried again in the oven. The product was dissolved in DMSO and purified by mass-directed automated HPLC.Product-containg fractions were concentrated under vacuum. The collected fractions were purified by SCX eluting with methanol and then with 2N NH3 / methanol.Ammonia fractions were combined. The solvent was evaporated in vacuo and the product was transformed into an hydrochloric acid salt by adding 2ml of DCM and 1 ml of hydrochloric acid in ether and the solution was left to stir during 1 h at RT. <n="96"/>The solvent was evaporated in vacuo, to give a pale yellow powder, 4-[2-chloro-3- (trifluoromethyl)phenyl]carbonyl}-1-[2-methyl-3-(6-methyl-3-pyridinyl)phenyl]-2- piperazinone (65 mg, 0.133 mmol, 25.3 % yield). [M+H]+ = 488.08, retention time = 1.74 minutes

Reference： [1]Patent: WO2009/53459,2009,A1 .Location in patent: Page/Page column 94-95

13
[ 1146412-38-5 ]
[ 659742-21-9 ]
[ 1146412-89-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 100℃; for 2h;Microwave irradiation;	Example 74^{^-chloro-S-ttrifluoromethylJphenyllcarbony^-i-^-methyl-S-ttheta-methyl-S- pyridinyl)phenyl]-2-piperazinone hydrochloride (E 74); <n="85"/>A mixture of 1-(5-bromo-2-methylphenyl)-4-[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-piperazinone (100mg, 0.210 mmol, prepared as described above for Example 53), <strong>[659742-21-9](6-methyl-3-pyridinyl)boronic acid</strong> (57.6 mg, 0.420 mmol) and sodium carbonate (1 11 mg, 1.051 mmol) in 1 ,2-Dimethoxyethane (DME) (2 ml) and Water (2.000 ml) was treated with Pd(Phi3P)4 (146 mg, 0.126 mmol) and the reaction mixture heated in the microwave at 1000C (high absorbtion) for 2 hours. The reaction mixture was diluted with EtOAc (15ml) and NaHCC>3 (sat., aq.) (15ml) and the product was extracted into EtOAc (x2). The combined organic layers were washed with water (15ml), brine (15ml) and then dried over magnesium sulphate. The solvent was evaporated in vacuo to give a dark brown oil.The crude product was purified by HPLC. Relevant fractions were combined and solvent evaporated in vacuo to give a colourless residue (the formate salt), which was dissolved in DCM (10ml) and NaHCtheta3 (sat., aq.). Product was extracted into the DCM and then the DCM was dried over magnesium sulphate and solvent evaporated in vacuo to give a white solid/ gum. This was dissolved in 1 ml DCM and treated with 0.5ml 1 M HCI in Et^O, and the reaction mixture stirred at RT for 30 minutes. The solvent was removed in vacuo and then co-evaporated with Et^O to give an off-white solid, 4-[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-1-[2-methyl-5- (6-methyl-3-pyridinyl)phenyl]-2-piperazinone. HCI (35mg, 0.060 mmol, 28.6 % yield), [M+H]+ 488, retention time 1.76 minutes.

Reference： [1]Patent: WO2009/53459,2009,A1 .Location in patent: Page/Page column 83-84

14
[ 1011722-02-3 ]
[ 659742-21-9 ]
[ 1011720-05-0 ]

Yield	Reaction Conditions	Operation in experiment
65%	With methanol; caesium carbonate;PS triphenylphosphine palladium resin; In 1,2-dimethoxyethane; at 120℃; for 1h;Microwave irradiation;	Example 29 3-(6-Methyl-3-pyridinyl)phenyl 5-thio-beta-D-xylopyranoside 500 mg (1.12 mmol) of 3-bromophenyl 2,3,4-tri-O-acetyl-5-thio-beta-D-xylopyranoside, obtained according to preparation VII, and 260 mg (1.68 mmol) of 6-methyl-3-pyridineboronic acid are placed in a suitable microwave reactor and then 500 mg of PS triphenylphosphine palladium resin (Argonaut) and 730 mg (2.24 mmol) of cesium carbonate are added. A mixture of 7 ml of dimethoxyethane and 3 ml of methanol is added and the reaction mixture is brought to 120 C. for 1 hour. After cooling, the reaction mixture is filtered and the filtrate is rinsed with methanol and concentrated under reduced pressure. The residue is purified by chromatography on a silica column, elution being carried out using a dichloromethane/methanol mixture (90/10; v/v), and then recrystallized from water. 3-(6-Methyl-3-pyridinyl)phenyl 5-thio-beta-D-xylopyranoside is obtained in the form of a white solid with a yield of 65%. M.p.=177 C. [alpha]D29=-89 (c=0.13; DMSO).

Reference： [1]Patent: US2009/186840,2009,A1 .Location in patent: Page/Page column 10

15
[ 1220700-80-0 ]
[ 659742-21-9 ]
[ 1220700-81-1 ]

Yield	Reaction Conditions	Operation in experiment
97%	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 90℃; for 3h;Sealed tube;	Step 5; A mixture of compound 54 (0.836 g, 2.00 mmol), 6-methylpyridin-3-ylboronic acid (0.548 g, 4.00 mmol), Pd(PPh3)2CI2 (85.1 mg, 0.12 mmol), and K2CO3 (0.829 g, 6.00 mmol) in dioxane/water (14/7 mL) was bubbled with nitrogen for 5 minutes, and heated in a sealed tube at 90 C to furnish a brown mixture. Heating was continued for 3 h, and LC-MS showed complete reaction. Water (40 mL) was added, and the mixture was vigorously stirred. The solid was collected by vacuum-filtration and further dried. The crude solid product was dissolved in MeOH/CH2CI2 (10/30 mL) and filtered through a pad of Celite to remove the insoluble materials. The filtrate containing compound 54 was used in the next step without further purification. LRMS m/z 475.2 (M+H)+.; Step iTo a mixture of compound 57 (0.500 g, 1.20 mmol), 6-methylpyridin-3-ylboronic acid (0.246 g, 1.5 mmol), Pd(PPh3)2CI2 (68.1 mg, 0.096 mmol), and K2CO3 (0.496 g, 3.59 mmol) in dioxane/water (10/5 ml_) was bubbled with nitrogen for 5 minutes. The resultant reaction solution was then heated in a sealed tube at 90 C to furnish a brown mixture. After the reaction mixture was heated for 3 h, LCMS showed the reacton was completed. Water (40 ml_) was added, and the mixture was vigorously stirred. The solid was collected by vacuum-filtration and further dried. The crude solid product was dissolved in MeOH/CH2CI2 (10/30 ml_) and filtered through a pad of Celite to remove the insoluble materials. The filtrate was concentrated in vacuo to give a solid which was triturated with MeOH, collected by vacuum-filtration, rinsed with MeOH, and further dried to afford compound 81 (568 mg, 97%). 1H NMR (400 MHz, CDCI3) delta 1.51 (s, 9 H) 1.62 - 1.82 (m, 2 H) 1.86 - 2.00 (m, 2 H) 2.67 (s, 3 H) 2.78 - 3.08 (m, 4 H) 3.62 (s, 3 H) 4.27 - 4.51 (m, 1 H) 7.39 (d, J=8.08 Hz, 1 H) 8.05 (d, J=8.84 Hz, 1 H) 8.34 - 8.44 (m, 1 H) 8.49 (d, J=9.09 Hz, 1 H) 8.74 (s, 1 H) 9.25 (s, 1 H).

Reference： [1]Patent: WO2010/38165,2010,A1 .Location in patent: Page/Page column 88; 102-103

16
[ 1240911-55-0 ]
[ 659742-21-9 ]
[ 1240911-56-1 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; copper(l) chloride;1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; In N,N-dimethyl-formamide; at 80℃; for 0.25h;Inert atmosphere;	(+/-)-6-Chloro- 5 -(4- iodobenzyl)-2-tetrahydro-2H-pyran-3-y l)-2,5 -d ihydro-3H-pyrazoo [4,3-c]cirmolin-3~one [(Example 66), 39 mg, 0.075 mtnol] was combined with (6-methylpyridin-3-yl) boronic acid (29 mg, 0.19 mmol, 2.5 equiv), copper(I) chloride (7.4 mg, 0.075 mmol, 1 equiv), cesium carbonate (49 mg, 0.15 mmol, 2 equiv), palladium(II) acetate (1.7 mg, 0.0075 mmol, 0.1 equiv), and bis(diphenylphosphino)ferrocene (4.2 mg, 0.0075 mmol, 0.1 equiv) in degassed N,N-dimethylformamide (1 mL). The mixture was placed into an oil bath preheated at 80 0C for 15 minutes, cooled to ambient temperature, diluted with water (5 mL) and extracted with ethyl acetate (3 X 30 mL). The combined organic extracts were washed three times with water and once with brine, dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 95:5; chloroform : methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) delta 8.66 (IH, s ), 8.21 (IH, d, J= 6.3 Hz), 7.70 (IH, d, J= 9.5 Hz), 7.64 (IH, d, J= 9.5 Hz), 7.49-7.40 (4H, m), 7.24-7.18 (2H, m), 6.32 (2H, s), 4.70-4.62 (IH, m), 4.05-3.95 (IH, m), 3.78 (IH, t, J - 10.1 Hz), 3.53-3.45 (IH, m), 2.58 (3H, s), 2.25-2.06 (IH, m), 1.90-1.80 (2H, m), 1.62-1.52 (2H, m) ppm; low resolution mass spectrometry (ES+) m/z 486.4 [(M+H)+; calculated for C27H25ClN5O2: 486.2].

Reference： [1]Patent: WO2010/96338,2010,A1 .Location in patent: Page/Page column 68

17
[ 1240911-55-0 ]
[ 659742-21-9 ]
ethyl 8-chloro-1-[(6'-methyl-2,3'-bipyridin-5-yl)methyl]-4-oxo-1,4-dihydrocinnoline-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; copper(l) chloride;1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; In N,N-dimethyl-formamide; at 95℃; for 0.25h;Inert atmosphere;	Ethyl l~[(6~bromopyridin-3-yl)methyl]-8-chloro-4-oxo-l,4- dihydrocinnoline-3-carboxylate (0.21 g, 0.49 mmol) was combined with (6-methylpyridin-3-yl) boronic acid (0.19 g, 1.2 mmol, 2.5 equiv), copper(I) chloride (48 mg, 0.49 mmol, 1 equiv), cesium carbonate (0,32 g, 0.97 mmol, 2 equiv), palladium(II) acetate (11 mg, 0.049 mmol, 0.1 equiv), and bis(diphenylphosphino)ferrocene (27 mg, 0.049 mmol, 0.1 equiv) in degassed N,N-dimethylformarnide (3 mL). The mixture was placed into an oil bath preheated at 95 0C for 15 minutes, cooled to ambient temperature, diluted with water (5 mL) and extracted with ethyl acetate (3 X 30 mL). The combined organic extracts were washed once with water and brine, dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound.

Reference： [1]Patent: WO2010/96338,2010,A1 .Location in patent: Page/Page column 70

18
[ 1240912-80-4 ]
[ 659742-21-9 ]
2-(2,3-dimethylphenyl)-5-[(6'-methyl-2,3'-bipyridin-5-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; copper(l) chloride;1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; In N,N-dimethyl-formamide; at 100℃; for 1h;	5-[(6~Bromopyridin-3-yl)methyl]-2-(2,3-dimethyIphenyl)- 2,5-dihydro-3H-pyrazolo[4,3-c]cmnoliti-3-one (0.10 g, 0.22 mmol), (6-methylpyrdin-3-yl)-boronic acid (74 mg, 0.54 mmol, 2.5 equiv), palladium(II)acetate (9.7 rag, 0.043 mmol, 0.2 equiv), 1,1'- bis(diphenylphosphino)ferrocene (24 mg, 0.043 mmol, 0.2 equiv), copper(l)chloride (21 mg, 0,22 mmol, 1 equiv) and cesium carbonate (0.18 g, 0.54 mmol, 2.5 equiv) were combined in N,N-dimethylformamide (4 mL) and placed into an oil bath preheated to 100 0C for 60 minutes. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (20 mL, aqueous saturated) and extracted with ethyl acetate (3 X 25 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (100:0 to 90:10; dichloromethane : methanol), providing the titled compound as a deep red solid: 1H-NMR (400 MHz, CDCl3) delta 9.06 (IH, d, J= 2.1 Hz), 8.78 (IH, d, J= 1.7 Hz), 8.32 (IH, dd, J= 7.8, LO Hz), 8.19 (IH, dd, J= 8.1, 2.3 Hz), 7.77 (IH, dd, J- 8.3, 2.4 Hz), 7.72 (IH, d, J= 8.3 Hz), 7.65-7.54 (3H, m), 7.42-7.38 (IH, m), 7.30-7.22 (3H? m), 5.90 (2H, s), 2.61 (3H, s), 2.37 (3H, s), 2.20 (3H5 s) ppm; high resolution mass spectrometry (ES+) m/z 473.2099 [(M+H)+; calculated for C29H25N6O: 473.2084].

Reference： [1]Patent: WO2010/96338,2010,A1 .Location in patent: Page/Page column 87

19
[ 1253115-19-3 ]
[ 659742-21-9 ]
[ 1253114-92-9 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; copper(l) chloride;1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; In N,N-dimethyl-formamide; at 90℃; for 0.5h;	(+/-)~5-[(4-Iodophenyl)methyl]-2-(tetrahydro-2//-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]thieno[2,3- e]pyridazin-3-one (50 mg, 0.10 mmol), cesium carbonate (66 mg? 0.20 mmol, 2 equiv), copper(I) chloride (10 mg, 0.10 mmol, 1 equiv), 2-methyl-5-pyridinylboronic acid (22 mg, 0.14 mmol, 1.4 equiv), palladium(II) acetate (2.3 mg, 10 mumol, 0.1 equiv), and 1,1'- bis(diphenylphosphino)ferrocene (11 mg, 20 mumol, 0.2 equiv) were combined in N1N- dimethylforraamide (3 niL) and placed into a preheated oil bath at 90 C for 30 minutes. The mixture was cooled to ambient temperature, poured into water (20 mL) and extracted with ethyl acetate (3 X 75 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexnaes : ethyl acetate containing 10% methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) delta 8.70 (IH, br s), 7.77 (IH, d, J = 8.2 Hz), 7.65 (IH, d, J= 5.6 Hz), 7.54 (2H, d, J = 8.3 Hz), 7.39 (2H, d, J = 8.3 Hz), 7.27-7.24 (2H, m), 5.81 (2H, s), 4.78-4.70 (IH, m), 4.02 (IH5 dd, J= 10.8, 3.9 Hz), 3.97 (IH, br d, J= 11.4 HzX 3.80 (IH, ap t, J = 10.5 Hz), 3.49 (IH, td, J- 11.3, 3.1 Hz), 2.62 (3H, s), 2.22 (IH, ddd, J = 17.2, 12.3, 5.0 Hz), 2.10 (IH, br d, J = 1 1.3 Hz), 1.94-1.80 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 458.1642' [(M+H)+; calculated for C25H24N5O2S: 458.1645

Reference： [1]Patent: WO2010/123716,2010,A1 .Location in patent: Page/Page column 55-56

20
[ 1253114-81-6 ]
[ 659742-21-9 ]
[ 1253114-82-7 ]

Yield	Reaction Conditions	Operation in experiment
	With water; caesium carbonate; copper(l) chloride;bis(tri-t-butylphosphine)palladium(0); In tetrahydrofuran; at 70℃; for 1.5h;	5 - [(6-Chlororhoyri din- 3 -y l)methy 1]-2-(2,3-dimethylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one [(Example 4), 47 mg, 0.11 mmol], cesium carbonate (92 mg, 0.28 mmol, 2,5 equiv), copper(I) chloride (11 mg, 0.11 mmol, 1 equiv), 2-methyl-5-pyridinylboronic acid (39 mg, 0.28 mmol, 2.5 equiv) and bis(tri~tert-butylphosphine)palladium(0) (11 mg, 0.023 mmol, 0.2 equiv) were combined in tetrahydrofuran (4 mL) and placed into a preheated oil bath at 70 0C. After 45 minutes, water (1 mL) was added and after 45 minutes, the mixture was poured into sodium bicarbonate (50 mL) and extracted with ethyl acetate (2 X 50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes : ethyl acetate containing 5% methanol), providing the titled compound as a deep red solid: 1H-NMR (400 MHz, CDCI3) delta 9.04 (IH, d, J = 1.4 Hz), 8.89 (IH, d, J= 2.3 Hz), 8.79 (IH, dd, J- 4.6, 1.7 Hz), 8.55 (IH, dd, J= 8.0, 1.8 Hz), 8.18 (IH, dd, J= 8.1 , 2.3 Hz), 8.03 (IH, dd, J = 8.2, 2.2 Hz), 7.70 (IH, d, J = 8.2 Hz), 7.52 (IH, dd, J= 8.0, 4.6 Hz), 7.27-7.25 (IH, m), 7.24-7.22 (3 H, m), 6.02 (2H, s), 2.61 (3H, s), 2.36 (3 H, s), 2.16 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 474.2043 [(M+H)+; calculated for C28H24N7O: 474.2037].

Reference： [1]Patent: WO2010/123716,2010,A1 .Location in patent: Page/Page column 37

21
[ 1253115-02-4 ]
[ 659742-21-9 ]
[ 1323190-03-9 ]

Yield	Reaction Conditions	Operation in experiment
	With water; caesium carbonate; copper(l) chloride;bis(tri-t-butylphosphine)palladium(0); In tetrahydrofuran; at 70℃; for 2h;	Ethyl l-[(6-chloropyridin-3-yl)rnethyl]~4- thioxo-l,4-dihydropytauido[2,3-c]pyridazine-3-carboxylate [(Example 5, Step 3), 335 mg, 0.972 mmol] was dissolved in tetrahydrofuran (15 mL), treated with an aqueous solution (3 mL) of cesium carbonate (792 mg, 2,43 mmol, 2.5 equiv), copper chloride (96.0 mg, 0.972 mrnol, 1 equiv), 2-methyl-5-pyridinylboronic acid (333 mg, 2.43 mmol, 2.5 equiv) and bis(t-tert- butylphosphine)palladium(O) (99.0 mg, 0.194 mmol, 0.2 equiv). The mixture was placed into a preheated oil bath at 70 0C for 2 hours, cooled to ambient temperature, poured into sodium bicarbonate (50 mL, aqueous saturated) and water (100 mL) and then extracted with ethyl acetate (2 X 75 mL), The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes : ethyl acetate containing 10% methanol), providing the titled compound as a light yellow solid.

Reference： [1]Patent: WO2010/123716,2010,A1 .Location in patent: Page/Page column 38

22
[ 1253115-10-4 ]
[ 659742-21-9 ]
[ 1253114-87-2 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; copper(l) chloride;1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; In N,N-dimethyl-formamide; at 100℃; for 1h;Inert atmosphere;	(+/-)-5 -[(4-Iodophenyl)methyl] -2-(tetrahydro-2H-pyran-3 -yl)-2,5 -dihydro-3/f- pyrazolo[4,3-c]rhoyrido[3,2-e]pyridazin-3-one [(Example 10, Step 3), 50 mg, 0.10 mmol], 2- methyl-5-pyridinylboronic acid (35 mg, 0.26 mmol, 2.5 equiv), palladium(II) acetate (4,6 mg, 0.21 mmol, 0.2 equiv), l5l'-bis(diphenylphosphino)ferrocene (11 mg, 0.21 mmol, 0.2 equiv), coprhoer(I) chloride (10 mg, 0.10 mmol, 1 equiv) and cesium carbonate (84 mg, 0.26 mmol, 2.5 equiv) were combined in degassed N, N-dimethylformamide (3 niL) and placed in a preheated oil bath at 100 0C for 1 hour. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (20 mL, aqueous saturated) and extracted with ethyl acetate (3 X 20 mL). The combined organic extracts were dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel gradient chromatography (100:0 to 90: 10; dichloromethane : methanol), providing the titled compound as a deep red solid: 1H-NMR (hydrochloride salt, 400 MHz, CDCl3) delta 8.78 (2H, br s), 8.59 (IH, d, J= 6.8 Hz), 8.39 (IH, br s), 7.72 (3H, br s), 7.55 (3H, br s), 6.02 (2H, s), 4.67 (IH, br s), 4.03-3.95 (2H, m), 3.79-3.70 (IH, m), 3.51-3.45 (IH, m), 3.02 (3H, br s), 2.36-2,06 (2H, m), 1.90-1.80 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 453.2039 [(M+H)+; calculated for C26H25N6O2: 453.2034].

Reference： [1]Patent: WO2010/123716,2010,A1 .Location in patent: Page/Page column 44

23
[ 953780-21-7 ]
[ 659742-21-9 ]
[ 1257638-67-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; ethanol; water; at 110℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	General procedure: Suzuki reaction / Sulfinamide Deprotection sequence (2 step) orSuzuki reaction / Sulfinamide Deprotection / Amide coupling / Boc deprotection sequence (4 step):(2S,3R)-2-Amino-3-hydroxy-N-[(R)-l-(6'-methyl-[3,3']bipyridinyl-6-yl)-ethyl]- butyramide trihydrochloride saltTo a mixture of (R)-2-methyl-propane-2-sulfinic acid [(R)-l-(5-bromo-pyridin-2-yl)- ethyl]-amide (500 mg, 1.64 mmol), 2-methylpyridine-5-boronic acid hydrate (305 mg, 2.0 mmol), K3PO4 (417 mg, 2.0 mmol), and Pd(dppf)Cl2'dichloromethane complex (133 mg, 0.16 mmol) in a microwave vial was added 3.3 mL of DME/H2O/EtOH (7:3:2). The vial was flushed with Ar, sealed and heated in the microwave at 110 0C for 20 min. The reaction was diluted with 30 mL water and 30 mL EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (2 x 25 mL). The combined organic layers were dried over MgStheta4 and concentrated to give a black oil. Purification by flash chromatography on silica gel (0->;5% MeOH/CH2Cl2) yielded 368 mg of 2- methyl-propane-2-(R)-sulfinic acid [(R)-l-(6'-methyl-[3,3']bipyridinyl-6-yl)-ethyl]- amide, as a brown crystalline solid, m/z 318.7 [M + H]+.

Reference： [1]Patent: WO2010/141273,2010,A1 .Location in patent: Page/Page column 62

24
[ 1312018-68-0 ]
[ 659742-21-9 ]
[ 1312019-16-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 100℃; for 2h;Microwave irradiation;	To a mixture of toluene-4-sulfonic acid-1-(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl ester (prepared as in Example 43, 0.15 g, 0.28 mmol), 2-methylpyridine-5-boronic acid hydrate (98 mg, 0.72 mmol) and dichlorobis(triphenylphosphine)palladium (II) (21 mg, 0.03 mmol) in dioxane (3 mL) was added an aqueous sodium carbonate solution (2 M, 0.36 mL). The resulting mixture was subjected to microwave irradiation for 2 h at 100 C. The mixture was diluted with ethyl acetate (100 mL), washed with a saturated aqueous sodium bicarbonate solution (2×30 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 50% ethyl acetate/hexanes) afforded 1-benzenesulfonyl-2-[2-cyclopentyl-1-(6-methyl-pyridin-3-yl)-vinyl-1H-pyrrolo[2,3-b]pyridine (100 mg, 78%) as a white solid: LC/MS m/e calcd for C26H25N3O2S [M+H]+ 444.57, observed 444.0.

Reference： [1]Patent: US2011/144105,2011,A1 .Location in patent: Page/Page column 51

25
[ 1339891-37-0 ]
[ 659742-21-9 ]
[ 1339888-46-8 ]

Yield	Reaction Conditions	Operation in experiment
34%	With potassium carbonate;sodium 2'?(dicyclohexylphosphaneyl)?2,6?diisopropyl?[1,1'?biphenyl]?3?sulfonate; palladium diacetate; In 1,4-dioxane; at 80℃; for 5h;Inert atmosphere;	Example 493-Cyclopropyl-3-f4-f7-(6-methyipyridm^vDpropanenitrile[00692] To 3-(4-(7-chloroimidazo[l,2-c]pyrimidin-5-yl)-lH-pyrazol-l-yl)-3- cyclopropyl-propanenitrile (Preparation M; 50 mg, 0.16 mmol) in dioxane (5 mL) was added K2CO3 (66 mg, 0.48 mmol), diacetoxypalladium (1.8 mg, 0.0080 mmol), 6-methylpyridin-3- ylboronic acid (44 mg, 0.32 mmol) and sodium 2'-(dicyclohexylphosphino)-2,6- dimethoxybiphenyl-3 -sulfonate (8.2 mg, 0.016 mmol). The reaction mixture was degassed with argon, sealed and heated to 80 C for 5 hours. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The residue was purified by silica gel chromatography (DCM/MeOH 10:1) to give the final product (20 mg, 34% yield). MS (apci) m/z = 370.2 (M+H).

Reference： [1]Patent: WO2011/130146,2011,A1 .Location in patent: Page/Page column 121

26
[ 1350643-73-0 ]
[ 659742-21-9 ]
[ 1350643-75-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; XPhos;palladium diacetate; In 1-methyl-pyrrolidin-2-one; at 160℃; for 1.5h;Inert atmosphere;	Compound 2 was converted to compound 26 according to the following Suzuki coupling procedure. 8-Chloro-2-phenyl-3-((S)-l-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino) ethyl)isoquinolin-l(2H)-one (2) (100 mg, 0.2 mmol, 1.0 eq), 6-methylpyridin-3-ylboronic acid (56 mg, 0.41 mmol, 2.0 eq), Pd(OAc)2 (9 mg, 0.04 mmol, 0.2 eq), 2-(dicyclohexylphosphino)-2',4',6'-triisopropylbiphenyl (58 mg, 0.12 mmol, 0.6 eq) and Na2C03 (64 mg, 0.6 mmol, 3.0 eq) were dissolved in l-methyl-2-pyrrolidinone (10 mL). The resulting mixture was degassed and backfilled with argon three times, and then stirred at 160 C under an argon atmosphere for 1.5 h. The reaction was complete based on TLC analysis. The mixture was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (1 :30 MeOH-DCM) to afford the product, 8-(6-methylpyridin-3-yl)-2-phenyl-3-((S)-l-(9- (tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)ethyl) isoquinolin-l(2H)-one (26); ESI-MS m/z : 558.30 [M+H]+.

Reference： [1]Patent: WO2011/146882,2011,A1 .Location in patent: Page/Page column 128

27
[ 1362850-84-7 ]
[ 343338-28-3 ]
[ 659742-21-9 ]
[ 1362851-01-1 ]

Yield	Reaction Conditions	Operation in experiment
41%		INTERMEDIATE 26 2-Methylpropane-2(6 -sulfinic acid N-[8-chloro-2-(6-methylpyridin-3-yl)quinolin-3-yll- meth-(E)-ylideneamideA mixture of Intermediate 9 (3.0 g, 9.1 mmol), 2-methylpyridin-5-ylboronic acid (1.24 g, 9.1 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.10 g, 0.1 mmol) in DME (60 mL) was treated with 2M aqueous Na2C03 solution (11 mL). The reaction mixture was degassed and flushed three times with nitrogen gas, then heated at 90C for 20 h. The mixture was allowed to cool to room temperature, and diluted with EtOAc (50 mL). The organic solution was washed with water (50 mL) and brine (50 mL), then dried (MgS04), and evaporated in vacuo. The resulting crude material was then treated with a mixture of titanium(IV) isopropoxide (5.4 mL, 18.0 mmol) and (5)-2-methyl-2-propane- sulfinamide (1.21 g, 10.0 mmol) in anhydrous THF (50 mL), according to the procedure described for Intermediate 2. The title compound (1.46 g, 41%) was obtained as a yellow gum. 5H (DMSO-d6) 9.17 (s, IH), 8.70 (d, J 1.9 Hz, IH), 8.61 (s, IH), 8.28 (dd, J 8.3, 1.1 Hz, IH), 8.11 (dd, J7.5, 1.3 Hz, IH), 8.00 (dd, J 7.9, 2.3 Hz, IH), 7.71 (dd, J 8.1, 7.7 Hz, IH), 7.50 (d, J 8.1 Hz, IH), 2.60 (s, 3H), 1.22 (s, 9H). LCMS (ES+) 386 (M+H)+, RT 1.65 minutes.

Reference： [1]Patent: WO2012/32334,2012,A1 .Location in patent: Page/Page column 36-37

28
[ 65753-47-1 ]
[ 659742-21-9 ]
[ 904310-94-7 ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water;Reflux;	100 g (0.676 mol) of 2,3-dichloropyridine was dissolved in 500 mL of ethanol, and 91.87 g (0.676 mol) of p-tolylboronic acid and 78 g (0.0676 mol) of Pd(PPh3)4 were sequentially added. A solution of 86 g (0.811 mol) of sodium carbonate in 500 mL of distilled water was placed in the reactor, and the mixture was heated to reflux for 4 ~ 6 hours so as to allow it to react. After completion of the reaction, the reaction solution was concentrated under reduced pressure to remove ethanol, and then extracted with ethyl acetate. The extract was treated with magnesium sulfate, filtered, and concentrated under reduced pressure, yielding 3-chloro-2-para-tolylpyridine as represented below in a 87% yield.

Reference： [1]Patent: WO2012/44043,2012,A2 .Location in patent: Page/Page column 18

29
[ 1367126-11-1 ]
[ 659742-21-9 ]
C₂₂H₂₂N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;copper diacetate; In dichloromethane; at 40℃; for 96h;Molecular sieve;	Compound Compound Example No. 27 Example No. 17 [0389] As described in Scheme 3, a mixture of compound 6 (200 mg, 1.0 eq.), compound 9a or 9b (1.1 eq., Combi-Blocks, LLC), triethylamine (4 eq.), Cu(OAc)2 (0.3 eq., Aldrich), and 4 A molecular sieves (0.4 g, Aldrich) in 10 mL of DCM was shaken at 40C for 96 h. After cooling to room temperature, the mixture was filtered, diluted with water (20 mL) and extracted with CHC13 (3 x 20 mL). The combined organic layers were concentrated.

Reference： [1]Patent: WO2012/35421,2012,A2 .Location in patent: Page/Page column 163-164

30
[ 1214908-78-7 ]
[ 659742-21-9 ]
[ 1214909-54-2 ]

Yield	Reaction Conditions	Operation in experiment
32%	With triethylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; methanol; at 140℃; for 0.5h;microwave oven; Inert atmosphere;	Example 73 The reaction was executed under an argon-atmosphere.To 100 mg (0.24 mmol) of example 33 and 90.0 mg (0.66 mmol) 6-methylpyridin-3-ylboronic acid, 3 mL dioxane and 1 mL methanol, 140 muL (1 mmol) TEA and 15 mg (0.02 mmol) 1,1'-bis(diphenylphosphino)ferrocenedichloropalladium(II) were added. The reaction mixture was heated to 140 C. for 30 min in a microwave oven. After cooling to room temperature the reaction mixture was filtered and the filtrate was evaporated under reduced pressure. The residue was purified by preparative HPLC (eluent A: water+0.13% TFA, eluent B: acetonitrile). 33.2 mg (32%) of the product were obtained.HPLC-MS (Method1): Rt=1.19 minMS (ESI pos): m/z=436 (M+H)+

Reference： [1]Patent: US2012/115863,2012,A1 .Location in patent: Page/Page column 77

31
[ 659742-21-9 ]
[ 109-06-8 ]
[ 21203-68-9 ]
[ 18699-87-1 ]
[ 57927-99-8 ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 4402 - 4413

32
[ 1383474-79-0 ]
[ 659742-21-9 ]
N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(6-methylpyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step C: Preparation of N-C3 -methyl- 1 -((6-methylpyridin-2-vQmethvO- 1 H- indazol-4-yl)-7-(6-methylpyridin-3-yl)imidazo[l,2-a]pyridine-3-carboxamide di- hydrochloride: 7-Bromo-N-(3-methyl- 1 -((6-methylpyridin-2-yl)methyl)- 1 H-indazol-4- yl)imidazo[l,2-a]pyridine-3-carboxamide (0.0486 g, 0.102 mmol) was dissolved in 2 mL of 1 : 1 DME:DMF. To this was added 6-methylpyridin-3-ylboronic acid (0.0210 g, 0.153 mmol), Pd(dppf)Cl2 (5 mol%>), and 2M aqueous sodium carbonate (153 mu, 0.306 mmol). Nitrogen was bubbled through the mixture for 5 minutes and the mixture was then heated to 90 C for 16 hours. The reaction mixture was diluted with EtOAc and the resulting precipitate was removed by filtration. The filtrate was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. Reverse phase chromatography of the crude material, followed by treatment with 4M HCl/dioxane gave the final product. MS (APCI), positive scan, m/z = 488.2 (M+H).

Reference： [1]Patent: WO2012/82689,2012,A1 .Location in patent: Page/Page column 103-104

33
[ 1383798-68-2 ]
[ 659742-21-9 ]
C₂₄H₂₇N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;polystyrene triphenylphosphine palladium(0); In 1,2-dimethoxyethane; water; at 100℃; for 1h;Microwave;	Step E: Synthesis of Examples 1.36-1.60 in Library FormatTo a mixture of the appropriate boronic acid (0.227 mmol) and polystyrene triphenylphosphine palladium(0) (0.009 mmol), was added a solution of methyl 6-(1-(4-iodophenyl)-3-methylbutylamino)nicotinate (80.0 mg, 0.19 mmol) in 1,2-dimethoxyethane (1.9 mL). Then aqueous potassium carbonate (0.95 mL, 1.9 mmol) was added. The reaction was heated for 1 hour at 100 C. in a microwave. The reaction was then filtered, the polymer was rinsed with tetrahydrofuran (3×2.0 mL), and the combined filtrates were concentrated.

Reference： [1]Patent: US2012/165343,2012,A1 .Location in patent: Page/Page column 31

34
[ 1391979-23-9 ]
[ 659742-21-9 ]
[ 1392099-57-8 ]

Yield	Reaction Conditions	Operation in experiment
43%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 120℃; for 1h;microwave irradiation;	To a mixture of 75 mg (0.21 mmol) E-l, 42 mg (0.31 mmol) (6-methylpyridine-3-yl) boronic acid, 54 mg (0.39 mmol) potassium carbonate and 0.11 mL water in 1 mL dioxane is added 24 mg (21 mu?iotaomicron) tetrakis(triphenylphospine)palladium(0) and the reaction mixture is stirred at 120C for 1 h under microwave irradiation. The product is purified with RP HPLC. Yield: 37.4 mg (43%). HPLC-MS: M+H = 408; tR = 0.98 min.
43%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 120℃; for 1h;Microwave irradiation;	To a mixture of 75 mg (0.21 mmol) E-1, 42 mg (0.31 mmol) (6-methylpyridine-3-yl) boronic acid, 54 mg (0.39 mmol) potassium carbonate and 0.11 mL water in 1 mL dioxane added 24 mg (21 mumol) tetrakis(triphenylphospine)palladium(0) and the reaction mixture is stirred at 120 C. for 1 h under microwave irradiation. The product is purified with RP HPLC. Yield: 37.4 mg (43%). HPLC-MS: M+H=408; tR=0.98 min

Reference： [1]Patent: WO2012/101184,2012,A1 .Location in patent: Page/Page column 70
[2]Patent: US2013/23533,2013,A1 .Location in patent: Paragraph 0296; 0297

35
[ 1391979-24-0 ]
[ 659742-21-9 ]
[ 1392099-63-6 ]

Yield	Reaction Conditions	Operation in experiment
14%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 130℃; for 0.5h;microwave irradiation;	To a mixture of 40 mg (89 mu?iotaomicron) E-2, 18 mg (0.13 mmol) (6-methylpyridine-3-yl) boronic acid, 27 mg (0.20 mmol) potassium carbonate and 0.2 mLwater in 1 mL DMF is added 7 mg (4 mu?iotaomicron) tetrakis(triphenylphospine)palladium(0) and the reaction mixture is stirred at 130C for 30 min under microwave irradiation. The product is purified with RP HPLC. Yield: 6.4 mg (14%). HPLC-MS: M+H = 506; tR = 1.21 min.
14%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 0.5h;Microwave irradiation;	To a mixture of 40 mg (89 mmol) E-2, 18 mg (0.13 mmol) (6-methylpyridine-3-yl) boronic acid, 27 mg (0.20 mmol) potassium carbonate and 0.2 mLwater in 1 mL DMF is added 7 mg (4 mumol) tetrakis(triphenylphospine)palladium(0) and the reaction mixture is stirred at 130 C. for 30 min. under microwave irradiation. The product is purified with RP HPLC. Yield: 6.4 mg (14%). HPLC-MS: M+H=506; tR=1.21 min

Reference： [1]Patent: WO2012/101184,2012,A1 .Location in patent: Page/Page column 73
[2]Patent: US2013/23533,2013,A1 .Location in patent: Paragraph 0308; 0309

36
[ 1400877-94-2 ]
[ 659742-21-9 ]
[ 1400877-15-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; at 120℃; for 0.333333h;Microwave irradiation;	Step 13 : (R)-2-(3-((3-carbamoyl-6-(6-methylpyridin-3-yl)pyrrolo[l,2-b]pyridazin-4- yl)ami -2-methylbutan-2-yl)oxazole-4-carboxamide[00305] PdCi2(dppf).CH2Ci2 adduct (1.8mg, 2.3muiotaetaomicron1) was added in one portion to a solution of (R)-2-(3-((6-bromo-3-carbamoylpyrrolo[l,2-b]pyridazin-4-yl)amino)- 2-methylbutan-2-yl)oxazole-4-carboxamide (lOmg, 0.023mmol), (6-methylpyridin-3- yl) boronic acid (6.5mg, 0.046mmol) and potassium phosphate solution (2M aqueous solution, 35mu, 0.069mmol). The reaction was then heated in the CEM microwave at 120 C for 20 min. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19 x 150 mm, 5-muiotaeta particles; Guard Column: Waters XBridge CI 8, 19 x 10 mm, 5-muiotaeta particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 5-100% B over 15 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of the product was 7.7 mg, and its estimated purity by LCMS analysis was 100%. Two analytical LC/MS injections were used to determine the final purity. Injection 1 conditions: Column: Waters Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7-muiotaeta particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50 C; Gradient: 0-100% B over 3 minutes, then a 0.75-minute hold at 100% B; Flow: 1.11 mL/min. Injection 2 conditions: Column: Waters Acquity UPLC BEH CI 8, 2.1 x 50 mm, 1.7-muiotaeta particles; Mobile Phase A: 5:95 acetonitrile:water with 0.05% TFA; Mobile Phase B: 95:5 acetonitrile:water with 0.05% TFA; Temperature: 50 C;Gradient: 0-100% B over 3 minutes, then a 0.75-minute hold at 100% B; Flow: 1.11 mL/min. XH NMR (500MHz, CD3OD) delta 8.68 (d, J=2.0 Hz, IH), 8.20 (s, IH), 8.09 (s, IH), 7.93 (dd, J=8.2, 2.2 Hz, IH), 7.89 (d, J=2.0 Hz, IH), 7.29 (d, J=7.9 Hz, IH), 7.13 (d, J=2.0 Hz, IH), 4.39-4.18 (m, IH), 1.56 (s, 3H), 1.52 (s, 3H), 1.35 (d, J=6.4 Hz, 3H).

Reference： [1]Patent: WO2012/125887,2012,A1 .Location in patent: Page/Page column 184-185

37
[ 1451042-78-6 ]
[ 659742-21-9 ]
[ 1032314-85-4 ]

Yield	Reaction Conditions	Operation in experiment
51%		To a suspension of 4-[(4-methyl-1 -piperazinyl)methyl]-N-[4-methyl-3-[(4- oxo-2-pyrimidinyl)amino]phenyl]benzamide (0.30 g, 0.69 mmol) in purified dioxane (15 ml) PyBrOP (0.34 g, 0.73 mmol) and triethylamine (0.29 ml, 2.1 mmol) were added under argon. The mixture was stirred at 45 C for 1.5 h. Then 6-methyl-3-pyridylboronic acid (0.10 g, 0.73 mmol) and Pd(PPh3)2Cl2 (24.3 mg, 5 mol-%) there were added and the reaction was stirred at ambient temperature for 1 h. After aqueous Na2CO3 solution (2.1 ml, 1 mol/L; 2.1 mmol) was transferred into mixture by syringe the reaction was refluxed for 24 h under argon. Reaction mixture diluted with ethyl acetate (30 ml) and brine (5 % solution) was filtered through celite. Organic phase was separated and dried. After evaporation of solvent under reduced pressure the residue was treated with methanol to obtain 0.18 g (51 %) of title compound. Analytical sample could be obtained by flash chromatography (EtOAc:MeOH 10: 1 followed by the eluent with addition of NH4OH). M.p. 202- 205C 1 H NMR (DMSO-ofe): 2.15 (s,3H), 2.21 (s,3H), 2.25- 2.45 (m, 8H), 2.52 (s,3H), 3.52 (s, 2H), 7.19 (d J= 8.5 Hz, 1 H) 7.37 (d J= 8.5 Hz, 1 H), 7.38 (d J= 5.2 Hz, 1 H), 7.43 (d J= 8.3 Hz, 2H), 7.48 (dd J= 8.2; 2.2 Hz, 1 H), 7.90 (d J= 8.3 Hz, 2H). 8.05 (d J= 2.0 Hz, 1 H), 8.36 (dd J= 8.2; 2.3 Hz, 1 H), 8.47 (d J=5.2 Hz, 1 H), 8.93 (s, 1 H), 9.14 (d J=2.3 Hz), 10.15 (s, 1 H).

Reference： [1]Patent: WO2013/120852,2013,A1 .Location in patent: Page/Page column 15; 16

38
[ 1025717-41-2 ]
[ 659742-21-9 ]
[ 1032314-38-7 ]

Yield	Reaction Conditions	Operation in experiment
46%		To suspension of 2-(2-methyl-5-nitrophenylamino)pyrimidin-4-one (0.20 g, 0.81 mmol) in anhydrous dioxane (10 ml) bromo-tris- pyrrolidinophosphonium hexafluoro-phosphate (PyBrOP, 0.46 g, 0.99 mmol) and triethylamine (0.33 ml, 2.37 mmol) were added under argon atmosphere. The mixture was stirred at room temperature for 2 h. The catalyst - bis(tri-phenylphosphine)-palladium(ll) chloride (29 mg, 5 mol-%) and 6-methyl-3-pyridyl boronic acid (0.13 g, 0.95 mmol) were added. After stirring for 0.5 h at room temperature Na2CO3 water solution (1 mol/L, 4.0 ml) was added dropwise and the mixture was refluxed for 24 h under argon. The mixture was evaporated till dryness, dissolved in ethyl acetate and washed with brine. Organic phase was dried and evaporated under reduced pressure. The product was subjected to flash chromatography on silica gel (dichloro methane: aceonitril 2: 1 ) to obtain 0.12 g (46%) of title compound, m.p. 172-173C. 1H NMR (DMSO-Ok): 2.43 (s, 3H), 2,54 (s, 3H), 7.42 (d, J= 8.4 Hz, 1 H), 7.52 (d J=8.3 Hz, 1 H), 7.55 (d J=5.2; 2.2 Hz, 1 H), 7.89 (dd J=8.4; 2.4 Hz, 1 H), 8.39 (dd J= 8.3; 2.2 Hz, 1 H), 8.60 (d J= 5.2 Hz, 1 H), 8.81 (d J= 2.4 Hz, 1 H), 9.22 (m, 2H).

Reference： [1]Patent: WO2013/120852,2013,A1 .Location in patent: Page/Page column 24; 25

39
[ 1414578-42-9 ]
[ 659742-21-9 ]
[ 1610374-09-8 ]

Yield	Reaction Conditions	Operation in experiment
64%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 95℃; for 18h;Sealed tube;	1005511 Step A: Preparation of 4-methyl-3-(6-methylpyridin-3-yl)-1-phenyl-1H- pyrazol-5-amine: 5-Amino-4-methyl- 1 -phenyl- 1 H-pyrazol-3 -yl trifluoromethane sulfonate [Preparation E] (1.01 g, 3.11 mmol), <strong>[659742-21-9](6-methylpyridin-3-yl)boronic acid</strong> (639 mg, 4.67 mmol), K2C03 (1.72 g, 12.45 mmol) and Pd(PPh3)4 (360 mg, 0.31 mmol) were combined in toluene (10 mL), water (5 mL) and EtOl-I (2.5 mL) and stirred at 95 C in a sealed tube for 18 hours. The cooled mixture was filtered through GF paper and the filtrate partitioned between water (50 mE) and EtOAc (50 mL). The aqueous layer was extracted with EtOAc (2 x 30 mE) and the combined organic phases were washed with brine (30 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica column chromatography eluting with 2% MeOHIDCM to afford 4-methyl-3-(6-methylpyridin-3-yl)- 1-phenyl-1H-pyrazol-5-amine (529 mg, 64% yield) as a red solid. MS (apci) m/z = 265.1 (M+H).

Reference： [1]Patent: WO2014/78323,2014,A1 .Location in patent: Paragraph 00551

40
[ 911113-15-0 ]
[ 659742-21-9 ]
[ 1611001-37-6 ]

Yield	Reaction Conditions	Operation in experiment
46.9%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In water; N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere;	The compound of example 93 (2.0 g, 9.01 mmol) was treated with 6-methylpyridin-3- ylboronic acid (1.480 g, 10.81 mmol) in DMF (10 mL) in presence of [1,1'- bis(diphenylphosphino)ferrocene]dichloro palladium(ll) complex with dichloromethane (0.221 g, 0.270 mmol) and sodium carbonate (1.909 g, 18.01 mmol) solution in 2 mL of water according to the procedure for the preparation of the compound of example 2 to afford the title compound. Yield: 1 .0 g (46.90 %) 1H NMR (DMSO, 300 MHz): delta 2.53 (s, 3H, CH3), 7.40 (d, 1 H, J = 8.4 Hz, Ar), 7.78 (d, 1 H, J = 1 .2 Hz, Ar), 8.06 (dd, 1 H, J = 8.1 Hz, J = 2.4 Hz, Ar), 8.143 (d, 1 H, J = 1 .2 Hz, Ar), 8.43 (d, 1 H, J = 1 .8 Hz, Ar), 8.85 (d, 1 H, J = 1 .8 Hz, Ar), 9.32 (d, 1 H, J = 1 .8 Hz, Ar); MS (ES+): m/e 235.1 (M+2H).

Reference： [1]Patent: WO2014/80241,2014,A1 .Location in patent: Page/Page column 67; 68

41
[ 1611000-85-1 ]
[ 659742-21-9 ]
[ 1610999-67-1 ]

Yield	Reaction Conditions	Operation in experiment
77%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere;	The compound of example 3 (0.2 g, 0.730 mmol) was treated with 2-methylpyridine-5- boronic acid (0.1 g, 0.730 mmol) in the presence of [1 ,1 '-bis(diphenylphosphino)- ferrocene]dichloropalladium(ll) complex with dichloromethane (0.018 g, 0.022 mmol) and sodium carbonate (0.155 g, 1 .42 mmol) according to the procedure for the preparation of the compound of example 2 to afford the title compound. Yield: 0.160 g (77 %); 1H NMR (DMSO-d6, 300 MHz): delta 2.56 (s, 3H, CH3), 7.34 (d, 1 H, J=8.1 , Ar), 7.45-7.52 (m, 1 H, Ar), 7.69 (d, 1 H, J=9.3, Ar), 7.78-7.88 (m, 2H, Ar), 8.1 -8.18 (m, 2H, Ar), 8.59 (d, 1 H, J=4.8, Ar); 8.73 (s, 1 H, Ar), 8.81 (s, 1 H, Ar), 8.96 (s, 1 H, Ar), MS (ES+): m/e 287 (M+1 ).

Reference： [1]Patent: WO2014/80241,2014,A1 .Location in patent: Page/Page column 41

42
[ 116355-18-1 ]
[ 659742-21-9 ]
[ 1611002-23-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere;	The compound of example 146 (8 g, 37.9 mmol) was treated with 6-methylpyridin-3- ylboronic acid (5.71 g, 41 .7 mmol) in the presence of [1 ,1 '-Bis(diphenylphosphino)- ferrocene]dichloropalladium(ll) complex with dichloromethane (0.495 g, 0.606 mmol) and sodium carbonate (6.03 g, 56.9 mmol) according to the procedure for the preparation of the compound of example 2 to afford the title compound. Yield: 8.0 g (95 %); 1 H NMR (DMSO-d6, 300 MHz): delta 2.2 (s, 3H, CH3), 2.54 (s, 3H, CH3), 7.35-7.37 (d, 1 H, J=8.1 Hz, Ar), 7.50-7.53 (d, 1 H, J=8.7 Hz Ar), 7.53 (s, 1 H, Ar), 7.76-7.80 (dd, 1 H, J=2.4 Hz & J=5.7 Hz, Ar Ar), 7.8 (s, 1 H, Ar), 8.4 (s, 1 H, Ar), 8.49-8.50 (d, 1 H, J=1 .8 Hz, Ar); MS (ES+): m/e 224.1 (M+1 ).

Reference： [1]Patent: WO2014/80241,2014,A1 .Location in patent: Page/Page column 127

43
[ 1417334-55-4 ]
[ 659742-21-9 ]
[ 1611001-73-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; 6-(6-methylpyridin-3-yl)-3-(4-morpholinophenyl)imidazo[1,2-a]pyridine-8-carbonitrile; In N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere;	The compound of example 172 (3 g, 1 1 .32 mmol) was treated with 2-methylpyridine-5- boronic acid (2.015 g, 14.72 mmol) in the presence of [1 ,1 '-bis(diphenylphosphino)- ferrocene]dichloropalladium(ll) complex with dichloromethane (0.159 g, 0.226 mmol) and sodium carbonate (2.347 g, 16.98 mmol) in dry dimethylformamide (10 mL) according to the procedure for the preparation of the compound of example 2 to afford the title compound. Yield: 3.0 g (91 %); 1 H NMR (DMSO-d6, 300 MHz): delta 2.51 (s, 3H, CH3), 7.40 (d, 1 H, J =8.1 Hz, Ar), 7.75 (s, 1 H, Ar), 8.026 (s, 1 H, Ar), 8.10 (dd, 1 H, J =3.0 Hz, J=8.1 Hz, Ar), 8.14 (s, 1 H, Ar), 8.86 (d, 1 H, J =3.0 Hz, Ar), 9.26 (s, 1 H, Ar); MS (ES+): m/e 278 (M+1 ).

Reference： [1]Patent: WO2014/80241,2014,A1 .Location in patent: Page/Page column 97

44
[ 474708-88-8 ]
[ 659742-21-9 ]
[ 1611002-17-5 ]

Yield	Reaction Conditions	Operation in experiment
61.7%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere;	The compound of example 245 (3 g, 12.96 mmol) was treated with 6-methylpyridin-3- ylboronic acid (2.130 g, 15.55 mmol) in the presence of [1 ,1 '-bis(diphenylphosphino)- ferrocene]dichloropalladium(ll) complex with dichloromethane (0.182 g, 0.259 mmol) and sodium carbonate (2.69 g, 19.44 mmol) in dry dimethylformamide (10 mL) according to the procedure for the preparation of the compound of example 2 to afford the title compound. Yield: 2.1 g (61.7 %); 1H NMR (DMSO-d6, 300 MHz): delta 2.51 (s, 3H, CH3), 7.37 (d, 1H, J =9.0 Hz, Ar), 7.67 (s, 1H, Ar), 7.86 (d, 1H, J =1.2 Hz, Ar), 8.04 (dd, J =3.0 Hz, J =8.1 Hz, 1H, Ar), 8.07 (d, 1H, J =0.9 Hz, Ar), 8.81 (d, 1H, J =2.4 Hz, Ar), 9.01 (d, 1 H, J =1.5 Hz, Ar); MS (ES+): m/e 244.6 (M+1 ).

Reference： [1]Patent: WO2014/80241,2014,A1 .Location in patent: Page/Page column 121

45
[ 217435-65-9 ]
[ 659742-21-9 ]
[ 1611001-10-5 ]

Yield	Reaction Conditions	Operation in experiment
71%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere;	The compound of example 30 (3.0 g, 14.21 mmol) was treated with (6-methylpyridin-3- yl)boronic acid (2.33 g, 17.06 mmol) in the presence of [1 ,1 '-bis(diphenylphosphino)- ferrocene]dichloropalladium(ll) complex with dichloromethane (0.348 g, 0.426 mmol) and sodium carbonate (3.0 g, 28.4 mmol) according to the procedure for the preparation of the compound of example 2 to afford the title compound. Yield: 2.25 g (71 %); 1 H NMR (DMSO-de, 300 MHz): delta 2.50 (s, 3H, CH3), 2.54 (s, 3H, CH3), 7.35 (d, 1 H, J=8.1 Hz, Ar), 7.43 (s, 1 H Ar), 7.56 (s, 1 H, Ar), 7.93 (s, 1 H, Ar), 7.99 (d, 1 H, J=8.1 Hz, Ar), 8.78-8.81 (m, 2H, Ar) ; MS (ES+): m/e 224 (M+1 ).

Reference： [1]Patent: WO2014/80241,2014,A1 .Location in patent: Page/Page column 48

46
[ 6188-23-4 ]
[ 659742-21-9 ]
[ 1611000-95-3 ]

Yield	Reaction Conditions	Operation in experiment
89%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In water; N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere;	The compound of example 1 (1 .0 g, 5.08 mmol) was treated with (6-methylpyridin-3- yl)boronic acid (0.695 g, 5.08 mmol) in the presence of dichlorobis(triphenylphosphine)palladium(l l) (0.286 g, 0.407 mmol) and potassium carbonate (0.701 g, 5.08 mmol) in dry dimethylformamide according to the procedure for the preparation of the compound of example 2 to afford the title compound. Yield: 0.950 g (89 %) ; MS (ES+) : m/e 21 0 (M+1 ).

Reference： [1]Patent: WO2014/80241,2014,A1 .Location in patent: Page/Page column 39; 40

47
[ 464192-28-7 ]
[ 659742-21-9 ]
2-(6-methylpyridin-3-yl)thiazole-5-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 110℃; for 0.333333h;Microwave irradiation;	Intermediate 11: 2-(6-methyl pyridin-3-yl)thiazole-5-carbaldehyde A mixture of <strong>[464192-28-7]2-bromothiazole-5-carbaldehyde</strong> (400 mg, 2.08 mmol), (6-methylpyridin-3- yl)boronic acid (428 mg, 3.12 mmol, 1.5 equiv), [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium(ll), complex with dichloromethane (170 mg,0.21 mmol, 0.1 equiv) and 2.0 M aqueous sodium carbonate (5.2 mL, 10.4 mmol, 5 equiv) in1,2-dimethoxyethane (6.9 mL) was heated in a microwave reactor at 110 00 for 20 minutes.The reaction was then diluted with ethyl acetate (50 mL) and water (50 mL). The layers wereseparated and the aqueous layer was extracted with ethyl acetate (2 x 25 mL). The combinedorganic extracts were washed with saturated aqueous sodium chloride (30 mL), dried overNa2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc) provided 2-(6- methylpyridin-3-yl)thiazole-5-carbaldehyde (0.176 g, brown solid) in 41% yield. 1H NMR (400 MHz, ODd3) oe 10.08 (5, 1H), 9.15 (d, J = 2.0 Hz, 1H), 8.47 (5, 1H), 8.19 (dd, J = 8.1, 2.4 Hz, 1 H), 7.31 (d, J = 8.3 Hz, 1 H), 2.66 (5, 3H). MS m/z 205.0 (M + H) Rt-0.36 mm.
41%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 110℃; for 0.333333h;Microwave irradiation;	A mixture of <strong>[464192-28-7]2-bromothiazole-5-carbaldehyde</strong> (400 mg, 2.08 mmol), (6-methylpyridin-3- yl)boronic acid (428 mg, 3.12 mmol, 1.5 equiv), [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium(ll), complex with dichloromethane (170 mg,0.21 mmol, 0.1 equiv) and 2.0 M aqueous sodium carbonate (5.2 mL, 10.4 mmol, 5 equiv) in1,2-dimethoxyethane (6.9 mL) was heated in a microwave reactor at 110 00 for 20 minutes.The reaction was then diluted with ethyl acetate (50 mL) and water (50 mL). The layers wereseparated and the aqueous layer was extracted with ethyl acetate (2 x 25 mL). The combinedorganic extracts were washed with saturated aqueous sodium chloride (30 mL), dried overNa2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc) provided 2-(6- methylpyridin-3-yl)thiazole-5-carbaldehyde (0.176 g, brown solid) in 41% yield. 1H NMR (400 MHz, ODd3) oe 10.08 (5, 1H), 9.15 (d, J = 2.0 Hz, 1H), 8.47 (5, 1H), 8.19 (dd, J = 8.1, 2.4 Hz, 1 H), 7.31 (d, J = 8.3 Hz, 1 H), 2.66 (5, 3H). MS m/z 205.0 (M + H) Rt-0.36 mm.

Reference： [1]Patent: WO2014/141153,2014,A1 .Location in patent: Page/Page column 46
[2]Patent: WO2014/141104,2014,A1 .Location in patent: Page/Page column 111

48
[ 1350607-38-3 ]
[ 659742-21-9 ]
[ 1350604-84-0 ]

Yield	Reaction Conditions	Operation in experiment
45%		General procedure: A glass microwave vesselwas chargedwith compound 60 (40 mg,0.128mmol), 4-(hydroxymethyl)phenylboronic acid (29 mg,0.192mmol), sodium carbonate (41 mg, 0.384 mmol), and dioxane/water (1.0mL:0.18 mL). The solution was purged with nitrogen for5 min, then Pd(PPh3)4 (15mg, 0.013 mmol) was added. The reactionmixture was stirred and heated at 120 C for 64 h. The reactionmixturewas filtered and washed with EtOAc/MeOH. The was concentratedand purified by reverse phase HPLC to give 21 mg (43%) ofthe title compound as an amorphous solid. .

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 6570 - 6585

49
[ 952399-42-7 ]
[ 659742-21-9 ]
1-(4-chlorobutyl)-6'-methyl-3,3'-bipyridin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium carbonate;palladium diacetate; triphenylphosphine; In 1,4-dioxane; at 20 - 80℃; for 27h;	Preparation 8: 1-(4-chlorobutyl)-6'-methyl-3,3l-bipyridin-2(1 H)-one (Prepdelta); 3-Bromo-1-(4-chlorobutyl)-2(1 H)-pyriotadiotanone (400 mg, 1 51 mmol and then 627 mg, 4 54 mmol) was added to a solution of (6-methyl-3-py?diotanyl)boroniotac acid (commercial Synchem OHG product list) (311 mg, 2 27 mmol) in dioxane (5 K2CO3 ml) The mixture was degassed bubbling with N2 for 10' and then triphenylphosphine (120 mg, 0 45 mmol) and palladium (II) acetate (34 mg, 0 15 mmol) were added The reaction mixture was stirred at reflux for 5 h and then at room temperature for 18 hours Further (6-methyl-3- py?diotanyl)boroniotac acid (Synchem OHG product list) (60 mg, 0 43 mmol), triphenylphosphine (78 mg, 0 3 mmol) and palladium (II) acetate (22 mg, 0 1 mmol) were added and the reaction was stirred for additional 4 hours at 800C The reaction was cooled and concentrated by removing the solvent under reduced pressure Water was added to the crude and the organic layers were extracted with DCM The organic layers were combined, dried over Na2SO4, filtered and concentrated in vacuo The crude product was purified by column chromatography on silica gel eluting with a gradient of methanol in DCM (from 0 to 5%) to afford the title compound (280 mg, 67%) 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 8 64 (br s , 1 H) 7 99 - 8 06 (m, 1 H) 7 59 - 7 69 (m, 1 H) 7 23 - 7 33 (m, 1 H) 7 1 1 - 7 20 (m, 1 H) 6 20 - 6 34 (m, 1 H) 3 94 - 4 07 (m, 2 H) 3 49 - 3 60 (m, 2 H) 2 5 (s, 3 H) 1 71 - 2 02 (m, 4 H)

Reference： [1]Patent: WO2007/113258,2007,A1 .Location in patent: Page/Page column 44

50
5-hydroxy-1-[5-iodo-4-(trifluoromethyl)-2-pyridyl]-3,4-dimethyl-imidazolidin-2-one [ No CAS ]
[ 659742-21-9 ]
C₁₇H₁₇F₃N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%		Exampl hyl)-2- pyridyl] 5-hydroxy-1-[5-iodo-4-(trifluoromethyl)-2-pyridyl]-3,4-dimethyl-imidazolidin-2-one (50 mg, 1 equiv. 0.125 mmol), <strong>[659742-21-9](6-methyl-3-pyridyl)boronic acid</strong> (22 mg, 1.1 equiv.), tricyclohexylphosphine (4 mg, 0.12 equiv.) tris(dibenzylideneacetone)dipalladium(0) (6 mg, 0.05 equiv.), in 1 ,4-dioxane (0.5 mL) was treated with K2C03 (38 mg) in water (0.2 mL). The reaction was heated for 80 minutes at 100C, then treated with further 6-methyl-3-pyridyl)boronic acid (2.2 equiv.), tricyclohexyl - - phosphine (4mg, 0.12 equiv.), tris(dibenzylideneacetone)dipalladium(0) (6 mg, 0.05 equiv), K3PO4 (45 mg, 1.7 equiv.) and the reaction was then heated for a further 75 minutes at 100C. The reaction mixture was diluted with EtOAc (6 mL) then filtered through celite, evaporated, then chromatographed on silica eluting with 20-100% EtOAc in isohexane. Fractions containing product were evaporated to give desired product as an amber gum (35 mg, 69%). LC-MS: (positive ES MH+ 367). H NMR (CDCI3): Major diastereomer: 8.69 (s, 1 H), 8.46 (s, 1 H), 8.21 (m, 1 H), 7.57 (dm, 1 H), 7.25 (dm, 1 H), 5.65 (m, 1 H), 4.91 (br s, 1 H), 3.56 (m, 1 H), 2.95 (s, 3H), 2.64 (s, 3H), 1.36 (d, 3H). Minor diastereomer: 8.69 (s, 1 H), 8.46 (s, 1 H), 8.21 (m, 1 H), 7.57 (dm, 1 H), 7.25 (dm, 1 H), 6.00 (d, 1 H), 4.78 (br s, 1 H), 3.79 (m, 1 H), 2.92 (s, 3H), 2. 64 (s, 3H), 1.42 (d, 3H).

Reference： [1]Patent: WO2015/52076,2015,A1 .Location in patent: Page/Page column 39; 40

51
8-bromo-N-(3-hydroxy-3-methylbutan-2-yl)pyrido[3,4-b]pyrazine-2-carboxamide [ No CAS ]
[ 659742-21-9 ]
N-(3-hydroxy-3-methylbutan-2-yl)-8-(6-methylpyridin-3-yl)pyrido[3,4-b]pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 80℃; for 1h;	In a 25 ml round-bottomed flask, 8-bromo-N-(3-hydroxy-3-methylbutan-2-yl)pyrido[4,3- b]pyrazine-2-carboxamide (50 mg, 147 muiotaetaomicron), 6-methylpyridin-3-ylboronic acid (20.2 mg, 147 muiotaetaomicron) and cesium carbonate (96.1 mg, 295 muiotaetaomicron) were combined with dioxane (10.0 ml) and water (1.0 ml) to give a light brown solution. Bis(diphenylphosphino)ferrocene- palladium(II)dichloride (10.8 mg, 14.7 muiotaetaomicron) was added. The reaction mixture was heated at 80 C for 1 hour. The crude reaction mixture was concentrated in vacuo and purified by chromatography (silica gel, ethyl acetate / heptane = 20:80 to 100:0) to yield the title compound (16 mg, 31 %) as light brown solid. MS: m/e = 352.3 [M+H]+.

Reference： [1]Patent: WO2015/71178,2015,A1 .Location in patent: Page/Page column 55

52
6-bromo-2-methylisoquinolin-1(2H)-one [ No CAS ]
[ 659742-21-9 ]
2-methyl-6-(6-methylpyridin-3-yl)isoquinolin-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.2%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium hydrogencarbonate; In 1,4-dioxane; at 110℃; for 1.5h;	A mixture of 6-bromo-2-methylisoquinolin-1-one (160 mg, 0.67 mmol), <strong>[659742-21-9](6-methylpyridin-3-yl)boronic acid</strong> (166 mg, 0.32 mmol), Pd(dppf)Cl2 (60 mg, 0.08 mmol) and saturated aqueous NaHCO3 (0.6 mL) in dioxane (6.5 mL) was microwaved at 110 C. for 1.5 h. Purification using silica gel chromatography (PE:EA=3:1 to 2:3) gave the title compound (160 mg, 95.2%) as a yellow solid. LCMS: 251.2 (M+H)+

Reference： [1]Patent: US2015/111885,2015,A1 .Location in patent: Paragraph 0483; 0484

53
(4S)-7-chloro-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b] [1,4]diazepine [ No CAS ]
[ 659742-21-9 ]
(4S)-7-(6-methylpyridin-3-yl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; water; at 10℃; for 8h;	To a degassed solution of (4S)-7-chloro-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine (10 g, 51.1 mmol), <strong>[659742-21-9](6-methylpyridin-3-yl)boronic acid</strong> (10.50 g, 77 mmol) and Potassium Phosphate Tri basic (21.70 g, 102 mmol) in 1,4-dioxane (100 mL) and water (20.0 mL) were added tris(dibenzylideneacetone)dipalladium(0) (4.68 g, 5.11 mmol) and x-phos (4.87 g, 10.22 mmol). The reaction mixture was heated at 100 C. for 8 h. The solvent was evaporated under reduced pressure; the obtained residue was diluted with water (200 ml) and extracted with DCM (2×100 ml). The combined organic layer was washed with water, brine, dried over sodium sulfate and solvent was evaporated under reduced pressure to obtain the crude product. The crude product was triturated with diethyl ether and n-pentane (1:1) for 3 times (3×100 mL) to afford (4S)-7-(6-methylpyridin-3-yl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine. (11.2 g, 44.4 mmol, 65%) as an off white solid (TLC: 10% MeOH in EtOAc Rf: 0.3). LCMS (m/z): 253.1 [M+H], Rt=2.86 min. 1H NMR (400 MHz, CDCl3): delta ppm 8.97 (d, J=2.19 Hz, 1H), 8.06 (dd, J=8.11, 2.41 Hz, 1H), 7.28-7.11 (m, 1H), 6.94 (d, J=7.89 Hz, 1H), 6.74 (d, J=7.67 Hz, 1H), 5.21 (s, 1H), 4.08-3.98 (m, 1H), 3.36-3.12 (m, 3H), 2.99-2.89 (m, 1H), 2.56 (s, 3H), 2.17-2.10 (m, 2H).
65%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; water; at 100℃; for 8h;	To a degassed solution of (4S)-7-chloro-2,3,4,5-tetrahydro-l,4-methanopyrido[2,3- £][l,4]diazepine (10 g, 51.1 mmol), <strong>[659742-21-9](6-methylpyridin-3-yl)boronic acid</strong> (10.50 g, 77 mmol) and Potassium Phosphate Tri basic (21.70 g, 102 mmol) in 1,4-dioxane (100 mL) and water (20.0 mL) were added tris(dibenzylideneacetone)dipalladium(0) (4.68 g, 5.11 mmol) and x-phos (4.87 g, 10.22 mmol). The reaction mixture was heated at 100 C for 8h. The solvent was evaporated under reduced pressure; the obtained residue was diluted with water (200 ml) and extracted with DCM (2x 100 ml). The combined organic layer was washed with water, brine, dried over sodium sulfate and solvent was evaporated under reduced pressure to obtain the crude product. The crude product was triturated with diethyl ether and n-pentane (1 : 1) for 3 times (3X100 mL) to afford (4S)-7-(6-methylpyridin-3-yl)- 2,3,4,5-tetrahydro-l,4-methanopyrido[2,3-b][l,4]diazepine. (1 1.2 g, 44.4 mmol, 65 %) as an off white solid (TLC: 10% MeOH in EtOAc Rf: 0.3). LCMS (m/z): 253.1 [M+H], Rt =2.86 min.1H NMR (400 MHz, CDC13): delta ppm 8.97 (d, J=2.19 Hz, 1 H), 8.06 (dd, J=8.1 1, 2.41 Hz, 1 H), 7.28 - 7.1 1 (m, 1 H), 6.94 (d, J=7.89 Hz, 1 H), 6.74 ( d, J=7.67 Hz, 1 H), 5.21 (s, 1 H), 4.08 - 3.98 (m, 1 H), 3.36 - 3.12 (m, 3 H), 2.99 - 2.89 (m, 1 H), 2.56 (s, 3 H), 2.17 - 2.10 (m, 2 H).

Reference： [1]Patent: US2015/152108,2015,A1 .Location in patent: Paragraph 0338; 0339; 0340
[2]Patent: WO2016/79709,2016,A1 .Location in patent: Page/Page column 145-146

54
C₁₉H₂₅BrN₂O₆S [ No CAS ]
[ 659742-21-9 ]
(R)-N-hydroxy-2-methyl-3-((R)-3-(4-(6-methylpyridin-3-yl)phenyl)-4,5-dihydroisoxazol-5-yl)-2-(methylsulfonyl)propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61.2%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; at 110℃; for 0.25h;Microwave irradiation;	General procedure: Method C: Synthesis of (R)-N-hydroxy-2-methyl-3-((R)-3-(4-(6-methylpyridin-3- yl)phenyl)-4,5-dihydroisoxazol-5-yl)-2-(methylsulfonyl)propanamide [67]

Reference： [1]Patent: WO2015/164458,2015,A1 .Location in patent: Page/Page column 112-113

55
[ 158326-84-2 ]
[ 659742-21-9 ]
3,3-dimethyl-6-(6-methylpyridin-3-yl)indolin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 115℃; for 6h;Inert atmosphere;	A mixture of 6-bromo-3,3-dimethylindolin-2-one (250 mg) from example la and 6- methylpyridine-3-boronic acid (214 mg) in 1,4-dioxane (4 ml) and aqueous sodium carbonate (1.3 ml) was flushed with argon, then [1,1?-bis(diphenylphosphino)ferrocene] dichloropalladium(II) (38 mg) was added and stirring was continued at 115 C for 6 h. The mixture was evaporated and the residue purified by flash chromatography (silica gel, gradient,10% to 100% EtOAc in n-heptane) to give the title compound (205 mg, 78%) as an off-white solid. MS (mlz): 253.3 [(M+H)41.

Reference： [1]Patent: WO2015/197567,2015,A1 .Location in patent: Page/Page column 27

56
2-[(3R)-3-methylmorpholin-4-yl]-8-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-1,7-naphthyridin-4-yl trifluoromethanesulfonate [ No CAS ]
[ 659742-21-9 ]
2-[(3R)-3-methylmorpholin-4-yl]-4-(6-methylpyridin-3-yl)-8-(1H-pyrazol-5-yl)-1,7-naphthyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%		Intermediate-b (0.10 g, 0.19 mmol) was solubilised in dioxane (1 ml). 2-Methyl-5- pyridinylboronic acid (52 mg, 0.38 mmol) was added in one portion followed by addition of caesium carbonate (0.25 g, 0.76 mmol) and PdCI2(dppf) in complex with dichloromethane (31 mg, 0.038 mmol). The reaction was heated for 4 hours in a sealed tube at 110C. The reaction was then cooled to rt and filtered. The solid was washed with ethyl acetate and the filtrate wasconcentrated under reduced pressure. The crude material was purified by preparative HPLC (acetonitrile/water/formic acid mixture). The combined fractions were concentrated under reduced pressure, solubilised in dichloromethane and 3N hydrochloric acid was added. The mixture was stirred overnight at rt and then quenched with a saturated aqueous solution of sodium hydrogen carbonate. The aqueous phase was extracted three times withdichloromethane. The organic phase was dried, filtered and concentrated under reduced pressure. The title compound was obtained in 53% yield (39 mg).?H-NMR (400MHz, DMSO-d5): 6 [ppm]= 1.29 (d, 3H), 2.59 (s, 3H), 3.35 - 3.42 (m, 1H), 3.56 (t, 1H),3.71 (d, 1H), 3.82 (d, 1H), 4.05 (d, 1H), 4.23 (d, 1H), 4.61 - 4.71 (m, 1H), 7.38 (d, 1H), 7.43 (s, 1H),7.47 (d, 2H), 7.63 (s, 1H), 7.92 (dd, 1H), 8.32 (d, 1H), 8.64 (d, 1H), 13.43 (s, 1H).

Reference： [1]Patent: WO2016/20320,2016,A1 .Location in patent: Page/Page column 239

57
[ 21921-76-6 ]
[ 659742-21-9 ]
4-(6-methylpyridin-3-yl)furan-2-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.2%		General procedure: Bromoarylaldehyde (1 mmol), aryl or alkenyl-boronicacid (1.2 mmol), and Cs2CO3(2.5 mmol) were dissolved orsuspended in a mixture of 1,4-dioxane (10 mL) and water (5 mL). The resulting mixture was stirred at RT for 5min. Tetrakis (triphenylphosphine) palladium(0) (0.05mmol) was added and the mixture was refluxed for 4-6 h under N2 protection. After cooling to RT, the mixture was dilutedwith CH2Cl2 (10 mL) and the separated aqueous layer wasextracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried over Na2SO4,filtered, and the solution was concentrated in vacuo to obtain a residue, whichwas purified by silica gel CC using ethyl acetate-petroleum ether gradientelution (1:200-1:4, v/v) to afford the aldehydes.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 1885 - 1888

58
5-chloro-3-(4-(methylsulfonyl)phenyl)pyridin-2-yl fluorosulfate [ No CAS ]
[ 659742-21-9 ]
[ 202409-33-4 ]

Reference： [1]Chemistry - A European Journal,2016,vol. 22,p. 5692 - 5697

59
methyl 4-[17-[(trifluoromethyl)sulfonyl]oxy}estra-1⁽¹⁰⁾,2,4,16-tetraen-3-yl]sulfonyl}butanoate [ No CAS ]
[ 659742-21-9 ]
4-[17-(6-methylpyridin-3-yl)estra-1,3,5⁽¹⁰⁾,16-tetraen-3-yl]sulfonyl}butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%		Example 15 4- [17-(6-methylpyridin-3-yl)estra-l ,3,5(10),16-tetraen-3-yl]sulfonyl}butanoic acid To 95 mg (0.17 mmol) methyl 4- [17- [(trifluoromethyl)sulfonyl]oxy}estra-l(10),2,4,16-tetraen-3- yl]sulfonyl}butanoate (Intermediate 5-A) in 2 ml dioxane 0.26 ml 2M aqueous sodium carbonate solution, 35 mg (0.26 mmol, 1.5 eq.) <strong>[659742-21-9](6-methylpyridin-3-yl)boronic acid</strong> and 12 mg dichlorobis(triphenylphosphine)palladium(II) (CAS No.: 13965-03-2) were added and the mixture was heated in a closed vessel at 90C. Then 0.4 ml 2M aqeous sodium hydroxide solution were added and the mixture was stirred for 17.5 h at 50C. The mixture was diluted with water, acidified by aqueous citric acid to pH 4, extracted three times with ethyl acetate, evaporated and purified by HPLC (method G) resulting in 36 mg (43% yield) of the title compound. LC-MS (method F): Rt = 0.93 min, m/z = 479.21. lH NMR (400 MHz, DMSO-d6): delta [ppm] = 1.02 (s, 3H), 1.43 - 1.83 (m), 1.91 - 2.00 (m, 1H), 2.09 - 2.21 (m, 2H), 2.26 - 2.49 (m), 2.94 - 3.04 (m, 2H), 3.24 - 3.32 (m), 6.06 - 6.1 1 (m, 1H), 7.22 (d, 1H), 7.55 - 7.65 (m, 3H), 7.70 (dd, 1H), 8.49 (d, 1H), 12.20 (br. s., 1H).

Reference： [1]Patent: WO2016/37956,2016,A1 .Location in patent: Page/Page column 69; 70

60
3-(6-bromo-7-cyano-3,4-dihydroquinolin-1(2H)-yl)-N-methyl-1-(tetrahydro-2H-pyran-4-yl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxamide [ No CAS ]
[ 659742-21-9 ]
3-[7-cyano-6-(6-methyl-3-pyridyl)-3,4-dihydro-2H-quinolin-1-yl]-N-methyl-1-tetrahydropyran-4-yl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); sodium carbonate; XPhos; In tetrahydrofuran; water; at 60℃; for 16h;Inert atmosphere;	tetrahydropyran-4-yl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5 -carboxamide (Intermediate N, 100 mg, 0.2 mmol) in THF (2.5 mL) and water (0.5 mL) was added chloro(2- dicyclohexylphosphino-2?,4?,6?-tri-i-propyl- 1,1 ?-biphenyl)(2?-amino- 1,1 ?-biphenyl-2-yl)palladium(1l) (16 mg, 0.02 mmol), 2-(dicyclohexylphosphino)-2?,4?,6?-triisopropylbiphenyl (10mg, 0.02 mmol), 6-methylpyridine-3-boronicacid (41 mg, 0.3 mmol) and Na2CO3 (42 mg, 0.4 mmol). The mixture was heated to 60C for 16 h under a nitrogen atmosphere. After cooling the reaction to room temperature, the mixture was filtered and concentrated in vacuo. DCM (50 mE) was added and the mixture was washed with water (30 mE x 3) and brine (30mE). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo.The crude residue was purified by reverse phase chromatography (acetonitrile 22-52% /0.05% NH4OH in water) to give the title compound (37 mg, 36%) as a white solid. ?H NMR(400 MHz, DMSO-d6) 6 8.55 - 8.54 (m, IH), 7.81 - 7.79 (m, IH), 7,35 - 7.33 (m, IH), 7.30(s, 1H), 6.78 (s, 1H), 6.56 - 6.55 (m, 1H), 4.38 - 4,25 (m, IH), 4.06 (s, 2H), 3.97 - 3.94 (m,2H), 3.64 - 3.58 (m, 4H), 3.49 - 3.43 (m, 2H), 2.93 - 2.90 (m, 2H), 2.78 - 2.72 (m, 2H), 2.55(d, J = 4.0 Hz, 3H), 2.52 (s, 3H), 2.02 - 1.92 (m, 4H), 1.85 - 1.82 (m, 2H). LCMS MZ(M+H) 512.

Reference： [1]Patent: WO2016/86200,2016,A1 .Location in patent: Page/Page column 432; 433

61
(4S)-7-chloro-8-fluoro-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine [ No CAS ]
[ 659742-21-9 ]
(4S)-8-fluoro-7-(6-methylpyridin-3-yl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; water; at 90℃; for 2.45h;	2,3,4,5-tetrahydro-l,4-methanopyrido[2,3-b][l,4]diazepine (200 mg, 0.936 mmol) & (6- methylpyridin-3-yl)boronic acid (167 mg, 1.217 mmol) in 1,4-dioxane (10 mL) and water (1 mL) then degassed for 15 min before adding x-phos (44.6 mg, 0.094 mmol) followed by addition of Pd2(dba)3 (42.9 mg, 0.047 mmol). The reaction was heated at 90 C for 2 h 45 min. The reaction mixture was cooled to RT, filtered through a pad of celite, washed with ethyl acetate (10 mL x2), and the solvent removed under reduced pressure. The organic compound was extracted with ethyl acetate (20 mL x2), washed with water (2 x 20 mL) and brine (20 mL). The extracts were dried over anhyd. Na2S04 and the solvent removed in vacuo to afford crude compound. The crude compound was purified by column chromatography using 100-200 silica gel and eluting with 1% MeOH in DCM to afford (4S)-8-fluoro-7-(6-methylpyridin-3-yl)-2,3,4,5-tetrahydro-l,4-methanopyrido[2,3- b][l,4]diazepine (220 mg, 0.705 mmol, 75 % yield) as an off-white solid, LCMS (m/z) 271.15 [M+H]+.

Reference： [1]Patent: WO2016/79709,2016,A1 .Location in patent: Page/Page column 144

62
(4S)-7-chloro-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine [ No CAS ]
[ 659742-21-9 ]
(4S)-7-(6-methylpyridin-3-yl)-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; water; at 100℃; for 7h;	To a degassed solution of (4,S)-7-chloro-8-(trifluoromethyl)-2, 3, 4, 5-tetrahydro-l,4- methanopyrido[2,3- ][l,4]diazepine (350 mg, 1.328 mmol), <strong>[659742-21-9](6-methylpyridin-3-yl)boronic acid</strong> (273 mg, 1.991 mmol) and K3PO4 (1096 mg, 3.98 mmol) in 1,4-dioxane (10 mL) and water (3 mL) were added Pd2(dba)3 (122 mg, 0.133 mmol) and x-phos (633 mg, 1.328 mmol). The reaction mixture was stirred at 100 C for 7 h. The reaction mixture allowed to room temperature and diluted with water (70 mL), extracted with ethyl acetate (3 X 150 mL). The combined organic layer was dried over anhydrous Na2S04 and concentrated under reduced pressure to give crude product. The crude mixture was triturated with pet ether (3x25 mL) and dried under vacuum to afford (4,S)-7-(6-methylpyridin-3-yl)-8- (trifluoromethyl)-2,3,4,5-tetrahydro-l,4-methanopyrido[2,3-^][l,4]diazepine (370 mg, 1.040 mmol, yield: 78 %) as an off white solid (TLC System: 5% Methanol in EtOAc, Rf: 0.3). LCMS (m/z) 320.90 [M+H]+.

Reference： [1]Patent: WO2016/79709,2016,A1 .Location in patent: Page/Page column 143-144

63
6-bromo-N-{2-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2H-indazol-5-yl}pyridine-2-carboxamide [ No CAS ]
[ 659742-21-9 ]
6'-methyl-N-{2-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2H-indazol-5-yl}-2,3'-bipyridine-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 105℃; for 1.5h;Microwave irradiation;	Example 21 6?-Methyl-N-{2-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2H-indazol-5-yl}-2,3?-bipyridine-6-carboxamide (1435) (1436) 75 mg (0.16 mmol) of 6-bromo-N-{2-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2H-indazol-5-yl}pyridine-2-carboxamide (Example 231) were dissolved in a degassed mixture of 1.73 ml of dioxane and 0.25 ml of water, and 45 mg (0.33 mmol) of <strong>[659742-21-9](6-methylpyridin-3-yl)boronic acid</strong>, 13 mg (0.02 mmol) of 1,1?-bis(diphenylphosphino)ferrocenepalladium(II) dichloride and 52 mg (0.49 mmol) of sodium carbonate were added. The reaction mixture was stirred in the microwave at 105 C. for 90 minutes. The reaction mixture was then filtered and saturated ammonium chloride solution and dichloromethane were added to the filtrate. The phases were separated and the organic phase was washed with saturated sodium chloride solution, filtered through a hydrophobic filter and concentrated. The crude product was dissolved in 2.5 ml of N,N-dimethylformamide and purified by preparative HPLC according to Method P1. The product fraction was lyophilized. This gave 40 mg (52% of theory) of the title compound. (1437) LC-MS (Method A3): Rt=0.46 min (1438) MS (ESIpos): m/z=470 (M+H)+ (1439) 1H NMR (300 MHz, DMSO-d6): delta=2.22 (s, 3H), 2.31 (br. s., 2H), 2.39 (br. s., 2H), 2.57 (s, 3H), 3.48 (br. s., 2H), 3.55 (d, 2H), 5.47 (s, 2H) 7.44 (d, 1H), 7.62 (s, 2H), 8.08-8.20 (m, 2H), 8.26-8.32 (m, 2H), 8.34 (s, 1H), 8.68 (dd, 1H), 9.43 (d, 1H), 10.54 (s, 1H).

Reference： [1]Patent: US2016/311833,2016,A1 .Location in patent: Paragraph 1435; 1436; 1437; 1438; 1439

64
(2R)-6-chloro-8-fluoro-2-methyl-4-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one [ No CAS ]
[ 659742-21-9 ]
(2R)-8-fluoro-2-methyl-6-(6-methylpyridin-3-yl)-4-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; XPhos; In 1,4-dioxane; water; at 100℃; for 3h;Inert atmosphere;	A solution of Intermediate 101 (340 mg, 1.01 mmol), (6-methylpyridin-3-yl)- boronic acid (165 mg, 1.21 mmol), 2M aqueous Na2C03 solution (1.51 mL) and X-Phos (24 mg, 0.05 mmol) in 1,4-dioxane (10 mL) was degassed withN2 for 10 minutes. Pd2(dba)3 (23 mg, 0.025 mmol) was added and the mixture was heated at 100C for 3 h, then cooled. The residue was diluted with EtOAc (10 mL) and the solids were removed by filtration through Kieselguhr. The filtrate was evaporated under reduced pressure. The resulting yellow solid was purified by column chromatography (Si02; gradient 0-6% MeOH/DCM) to give the title compound (168 mg, 38%). Method B HPLC-MS: MH+ mlz 395, RT 1.49 minutes (85%).

Reference： [1]Patent: WO2016/198400,2016,A1 .Location in patent: Page/Page column 167

65
9-bromo-7-(4-chlorophenyl)-1-methyl-6,7-dihydro-5H-benzo[f][1,2,3] triazolo[1,5-d][1,4]diazepine [ No CAS ]
[ 659742-21-9 ]
7-(4-chlorophenyl)-1-methyl-9-(6-methylpyridin-3-yl)-6,7-dihydro-5H-benzo[f][1,2,3]triazolo[1,5-d][1,4]diazepine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 120℃; for 1h;Inert atmosphere;	A mixture of 9-bromo-7-(4-chlorophenyl)-1-methyl-6,7-dihydro-5H-benzo[f][1,2,3]triazolo[1,5-d][1,4]diazepine (80 mg, 0.2 mmol), <strong>[659742-21-9](6-methylpyridin-3-yl)boronic acid</strong> (28 mg, 0.2 mmol), Pd(PPh3)4 (24 mg, 0.02 mmol), K3PO4 (168 mg, 0.63 mmol) in DME (16 mL) and H2O (0.2 mL) were stirred at 120 C for 1 h under N2. The solvent was removed under reduced pressure to give a residue which was purified by preparative TLC (eluent: petroleum ether: ethyl acetate=1 : 1) to give 7-(4-chlorophenyl)-1-methyl-9-(6-methylpyridin-3-yl)-6,7-dihydro-5H-benzo[f][1,2,3]triazolo[1,5-d][1,4]diazepine as a white solid (8 mg, 10%). LCMS (Method B): 3.07 min m/z [MH]+=402.1, 404.1.

Reference： [1]Patent: WO2017/20086,2017,A1 .Location in patent: Page/Page column 66
[2]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 1298 - 1303

66
[ 202409-81-2 ]
[ 659742-21-9 ]
[ 202409-33-4 ]

Yield	Reaction Conditions	Operation in experiment
55%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In 1,4-dioxane; for 20h;Inert atmosphere; Reflux;	In a 500 mL single-necked flask,Bromo-5-chloro-3- (4- (methylsulfonyl) phenyl) pyridine (17.4 g, 0.050 mol)Was dissolved in 1,4-dioxane (100 mL)Cesium fluoride (15.2 g, 0.100 mol) was added successively,Cuprous iodide (1.0 g, 0.005 mol)2-methyl-5-pyridineboronic acid (20.6 g, 0.150 mol)And tetrakis (triphenylphosphine) palladium (0.6 g, 0.001 mol)The reaction was refluxed under N2 for 20 h. Reaction finished,The reaction was quenched with water, cooled, filtered, extracted with ethyl acetate (100 mL x 3)The extract was washed with saturated sodium chloride solution (50 mL x 1), dried over anhydrous sodium sulfate,The solvent was distilled off under reduced pressure, the residue was beaten with a small amount of isopropyl ether,The residue was dried to give 29.7 g of the desired product 5-chloro-6'-methyl-3- (4- (methylsulfonyl) phenyl) -2,3'-bipyridine in a yield of 55%.

Reference： [1]Patent: CN106632002,2017,A .Location in patent: Paragraph 0074; 0081; 0082; 0083; 0101; 0102; 0103

67
[ 687636-93-7 ]
[ 659742-21-9 ]
[2-(6-methylpyridin-3-yl)-1,3-thiazol-5-yl]methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); caesium carbonate; In tetrahydrofuran; water; at 80℃; for 3h;Inert atmosphere;	<strong>[687636-93-7]2-bromothiazole-5-methanol</strong>(20 g, 0.103 mol, 1 eq.),2-methylpyridine-5-acid (18.3 g, 0.134 mol, 1.3 eq.),ATAphos*PdCl2 (3.65 g, 5.152 mmol, 0.05 eq.),Cs2CO3 (67.14 g, 0.206 mol, 2 eq.) was dissolved in THF (800 ml) and water (800 ml). The mixture was flushed with nitrogen and stirred at 80 C for 3 hours. The mixture was cooled to room temperature and diluted with EEO (300 ml). The layers were separated and the aqueous layer was extracted with EEO (3 x 100 ml) and the combined organic layers were dried over MgSO4 and evaporated after filtration. The residue was crystallized from EEO/DIPO, filtered and dried in vacuo to give a brown solid.

Reference： [1]Patent: TW2018/2094,2018,A .Location in patent: Page/Page column 54

68
C₂₀H₂₀ClFN₂O [ No CAS ]
[ 659742-21-9 ]
C₂₆H₂₆FN₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 110℃; for 2h;Sealed tube; Microwave irradiation;	A mixture of compound 179 (150 mg, 0.42 mmol), 2-methylpyridine-5- boronic acid (86 mg, 0.63 mmol), sodium carbonate (133 mg, 1.25 mmol), 1,4-dioxane (1.5 mL) and water (0.5 mL) in a vial was sparged with nitrogen for 5 min. [ 1, 1 '- Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (31 mg, 0.042 mmol) was added. The nitrogen sparging was continued for another 2 min. The vial was sealed, and heated in a Biotage microwave synthesizer at 1 10 C for 2 h. After the reaction was cooled to room temperature, EtOAc was added. The mixture was filtered through a plug of Celite, and eluted with EtOAc. The filtrate was concentrated. The residue was purified by flash chromatography (silica gel, eluting with 0% to 60% EtOAc in hexanes) to give compound 194b (132 mg, 76% yield) as a pink foamy solid, m/z = 416 (M+l).

Reference： [1]Patent: WO2018/111315,2018,A1 .Location in patent: Page/Page column 88; 117; 257; 258

69
1-(5-chloro-2-ethoxy-3-iodo-4-methylphenyl)ethan-1-ol [ No CAS ]
[ 659742-21-9 ]
1-(5-chloro-2-ethoxy-4-methyl-3-(6-methylpyridin-3-yl)phenyl)ethan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.77%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere;	1- (5-chloro-2-ethoxy-3-iodo-4-methylphenyl) ethan-1-ol (5 g, 14.7 mmol) , (6-methylpyridin-3-yl) boronic acid (2.42 g, 17.6 mmol) , Pd (PPh 3) 4 (85 mg, 0.734 mmol) and K 2CO 3 (6.1 g, 44 mmol) were dissolved in 1, 4-dixoane (30 mL) /H 2O (20 mL) and heated to 100 under N 2 for overnight. Solvent was removed and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over Na 2SO 4. The product (4.3 g in 95.77 %yield) was got by chromatography column on silica gel (CH 2Cl 2/MeOH=50/1) . 1H NMR (400 MHz, DMSO-d6) delta 8.32 (d, J = 1.7 Hz, 1H) , 7.64 -7.58 (m, 1H) , 7.52 (s, 1H) , 7.35 (d, J = 7.9 Hz, 1H) , 5.20 (d, J = 4.5 Hz, 1H) , 5.07 -4.86 (m, 1H) , 3.54 -3.37 (m, 1H) , 2.53 (s, 3H) , 2.04 (s, 3H) , 1.34 (t, J = 6.4 Hz, 3H) , 0.84 (t, J = 7.0 Hz, 3H) . MS (ESI) m/e (M+1) +306.

Reference： [1]Patent: WO2018/103688,2018,A1 .Location in patent: Paragraph 0142; 0143

70
C₁₈H₁₇IN₆O₂ [ No CAS ]
[ 659742-21-9 ]
N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1,2,6'-trimethyl-6-oxo-1,6-dihydro-[3,3'-bipyridine]-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 80℃; for 16h;Inert atmosphere;	[0630] A solution ofExample 155e (0.13 g, 0.27 mmol), Example 155f (40 mg, 0.27 mmol), Pd(dppf)Cl2 (20 mg, 0.03 mmol) and Na2C03(87 mg, 0.82 mmol) in Dioxane/H20 (3 mL/1 mL) was stirred at 80C for 16 h under N2. The reaction mixture was concentrated under reduced pressure, which was purified by silica gel chromatography (DCM MeOH = 50: 1 to 20: 1), followed by Prep-HPLC (by Ultimate XB-C18, 50 x 250 mm, 10 mupiiota, speed: 80 mL/min, eluent: H20/CH3CN = from 80/20 to 20/80 over 50 min) purification to give the desired product Example 155 (54 mg, yield 45%) as a white solid.LCMS [M+l] + = 442.0 [0631] 'HNMR (400 MHz, DMSO-d6delta 12.68 (s, 1H), 8.66 (s, 1H),8.43 (d, J= 2.4 Hz, 1H), 8.36-8.32 (m, 1H), 8.28 (s, 1H), 8.00 (t, J= 8.0 Hz, 1H), 7.83 (dd, J= 7.6, 0.9 Hz, 1H), 7.69 (dd, J= 7.9, 2.4 Hz, 1H), 7.36 (d, J= 8.0 Hz, 1H), 3.80 (tt, J= 7.5, 4.0 Hz, 1H), 3.69 (s, 3H), 2.52 (s, 3H), 2.43 (s, 3H), 1.18- 1.12 (m, 2H), 1.06-1.01 (m, 2H).

Reference： [1]Patent: WO2018/151830,2018,A1 .Location in patent: Paragraph 0630-0631

71
C₇H₆INO₃ [ No CAS ]
[ 659742-21-9 ]
C₁₃H₁₂N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 85℃; for 16h;Inert atmosphere;	[0614] A mixture of Example 149c (2.0 g, 7.2 mmol), Example 149d (1.0 g, 7.2 mmol), Pd(dppf)Cl2(520 mg, 0.72 mmol) and Cs2C03 (7.0 g, 21.5 mmol) in dioxane/H20 (30 mL/2.5 mL) was exchanged with N2 for 3 times, and then stirred at 85C for 16 h at N2.The mixture was concentrated under reduced pressure, and purified by silica gel chromatography (DCM/MeOH = 50/1 to 20/1) to give the desired product Example 149e (1.8 g, yield 100%) as a brown solid.LCMS [M+l]+ = 244.9

Reference： [1]Patent: WO2018/151830,2018,A1 .Location in patent: Paragraph 0614; 0633

72
5-iodo-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carboxamide [ No CAS ]
[ 659742-21-9 ]
N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1,2,6'-trimethyl-6-oxo-1,6-dihydro-[3,3'-bipyridine]-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 80℃; for 16h;Inert atmosphere;	[0626] A solution ofExample 154e (0.14 g, 0.29 mmol),Example 154f (40 mg, 0.29 mmol), Pd(dppf)Cl2 (22 mg, 0.029 mmol) and Na2C03(93 mg, 0.87 mmol) in Dioxane/H20 (3 mL/1 mL) was stirred at 80C for 16 h under N2. The reaction mixture was concentrated under reduced pressure, which was purified by silica gel chromatography (DCM/MeOH = 50: 1 to 20: 1), followed by Prep-HPLC (by Ultimate XB-C18, 50 x 250 mm, 10 mum, speed: 80 mL/min, eluent: H20/CH3CN = from 80/20 to 20/80 over 50 min)purification to get the desired product Example 154 (50 mg, yield 45%) as a white solid.LCMS [M+1] + =444.1 1H NMR (400 MHz, DMSO-d6) 6 delta 12.69 (s, 1H), 8.88 (s, 1H), 8.43 (d, J= 2.4 Hz, 1H), 8.34 (d, J= 8.2 Hz, 1H), 8.28 (s, 1H), 8.01 (t, J= 8.0 Hz, 1H), 7.80 (d, J= 7.6 Hz, 1H), 7.69 (dd, J= 8.0, 2.4 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 5.30 (p, J= 6.7 Hz, 1H), 3.7 (s, 3H), 2.52 (s, 3H), 2.43 (s, 3H), 1.53 (d, J= 6.7 Hz, 6H).

Reference： [1]Patent: WO2018/151830,2018,A1 .Location in patent: Paragraph 0626

73
[ 461-89-2 ]
[ 659742-21-9 ]
2-(6-methylpyridin-3-yl)-1,2,4-triazine-3,5(2H,4H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With oxygen; copper diacetate; triethylamine; In N,N-dimethyl-formamide; at 65℃; for 4h;	General procedure: To a solution of <strong>[461-89-2]6-azauracil</strong> (100 mg, 0.88 mmol) inDMF (10.0 mL) was added base (1.76 mmol) and Cu(OAc) 2(159 mg, 0.88 mmol) at room temperature. The resulting reationmixture was degassed with oxygen for 10 min and then addedarylboronic acids (0.96 mmol) at room temperature and stirredat appropriate temperature (Table-1) under oxygen atmosphere.The reaction mixture was diluted with water (15 mL) andextracted with dichloromethane (3 × 15 mL). The organic layerwashed with H 2 O (15 mL), brine solution (15 mL), dried overNa 2 SO 4 and concentrated. The obtained crude product waspurified by column chromatography (0 to 10 % CH 3 OH/CH 2 Cl 2 )to afford the title compounds.

Reference： [1]Asian Journal of Chemistry,2018,vol. 30,p. 2495 - 2501

74
55-bromo-54-fluoro-14H-6-oxa-3-aza-2(2,6)-pyridina-1(3,4)-triazola-5(1,2)-benzenacyclodecaphan-4-one [ No CAS ]
[ 659742-21-9 ]
54-fluoro-55-(6-methylpyridin-3-yl)-14H-6-oxa-3-aza-2(2,6)-pyridina-1(3,4)-triazola-5(1,2)-benzenacyclodecaphan-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 4h;	A mixture of 55-bromo-54-fluoro- l4H-6-oxa-3-aza-2(2,6)-pyridina- l(3,4)-triazola-5(l,2)- benzenacyclodecaphan-4-one (80 mg, 0.18 mmol), <strong>[659742-21-9](6-methylpyridin-3-yl)boronic acid</strong> (38 mg, 0.28 mmol), Pd(dppf)Cl2 (40 mg, 0.05 mmol) and K2C03 (51 mg, 0.37 mmol) in dioxane/H20 (3 mL, 10/1) was stirred at 90 C for 4 h. After this time the mixture was concentrated and purified by column chromatography on silica gel using petroleum ether/EtOAc (100/1) followed by DCM/MeOH (100/1 to 10/1) as eluents to give the title compound (40 mg, 49%) as a white solid. 1H NMR (400 MHz, DMSO- 6) delta ppm 11.06 (s, 1H), 8.58 - 8.71 (m, 2H), 8.01 - 8.12 (m, 2H), 7.82 - 7.90 (m, 3H), 7.34 - 7.43 (m, 2H), 4.37 (m, 2H), 4.20 - 4.29 (m, 2H), 2.51 (m, 5H), 1.95 (m, 2H). MS (ESI): 445.1 [M + H]+.
43.4 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 95℃; for 16h;Inert atmosphere;	[00406] To a mixture of Example 64e (200 mg, 0.46 mmol), Example 64f (60 mg, 0.48 mmol), and Na2C03 (138 mg, 1.30 mmol) in dioxane/H20 (4 mL/2 mL) was added Pd(dppf)Cl2(32 mg, 0.04 mmol). The resulting mixture was degassed by bubbling N2 through the solution for 2 min, which was then heated at 95C for 16 h. The mixture was directly purified by silica gel chromatography (DCM/MeOH = 50/1 to 10/1) to give the desired product Example 64 (43.4 mg, yield 21%) as a white solid. LCMS [M+l]+ = 445.0. NMR OO MHz, DMSO- 6) delta 11.06 (s, 1H), 8.67 (s, 1H), 8.61 (s, 1H), 8.12-8.02 (m, 2H), 7.89-7.84 (m, 3H), 7.42-7.34 (m, 2H), 4.37 (t, J= 5.1Hz, 2H), 4.29-4.22 (m, 2H), 2.51 (s, 3H), 2.47-2.51 (m, 2H),1.95 (m, 2H).

Reference： [1]Patent: WO2018/148204,2018,A1 .Location in patent: Page/Page column 74
[2]Patent: WO2019/51265,2019,A1 .Location in patent: Paragraph 00406; 00403

75
[ 886230-74-6 ]
[ 659742-21-9 ]
3-(6-methylpyridin-3-yl)-6-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃; for 12h;Inert atmosphere;	General procedure: To a mixture of 53 (0.75g, 2.0mmol) and 183 1,4-dioxane/184 H2O (20mL, v/v, 5:1) were added 185 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (0.49g, 2.4mmol), 186 K2CO3 (0.83g, 6.0mmol) and 187 Pd(PPh3)4 (0.23g, 0.2mmol). The reaction mixture was placed into an oil bath preheated to 90C and stirred at this temperature for 12h under argon. Then the reaction mixture was cooled to rt before pouring into 140 water (20mL). The mixture was extracted by 80 EtOAc (50mL) and washed with water (50mL) followed by brine (50mL). The organic layers were dried over sodium sulfate, filtered, concentrated and purified by silica gel column chromatography (eluting with 0-20% EtOAc in 165 heptane) to afford 188 54a (0.54g, 83%) as a yellow solid. 1H NMR (400MHz, DMSO-d6) delta 8.81 (s, 1H), 8.31 (d, J=8.8Hz, 1H), 8.07 (d, J=6.8Hz, 1H), 8.00 (d, J=6.6Hz, 2H), 7.58 (s, 2H), 7.50 (s, 1H), 6.20 (d, J=6.8Hz, 1H), 3.91 (s, 2H), 2.49-2.41 (m, 1H), 2.09 (s, 2H), 1.80 (s, 1H), 1.63 (s, 2H); LC/MS (ESI, m/z) 324.14 [M+ H]+.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 160,p. 61 - 81
[2]Journal of Medicinal Chemistry,2019,vol. 62,p. 5006 - 5024

76
[ 106-38-7 ]
[ 659742-21-9 ]
[ 30456-56-5 ]

Yield	Reaction Conditions	Operation in experiment
78%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 50℃; for 5h;Inert atmosphere;	General procedure: To an oven dried 5 mL microwave vessel was addedPd(dppf)Cl2·CH2Cl2 (4 mol%), halide/pseudohalide (1 equiv),boron coupling partner (1 equiv), and Cs2CO3 (3 equiv). Thevessel was then capped and purged with N2 before addition ofCyrene (1 mL, 0.25 M) and H2O (1.8 mL). The reaction mixturewas heated to 50 C and maintained at this temperature withstirring for 5 h before the vessel was vented and decapped. Thesolution was then diluted with Et2O (10 mL) and washed withwater (2 × 20 mL) and brine (2 × 20 mL). The organics were thenpassed through a hydrophobic frit and concentrated underreduced pressure to give a residue, which was purified by flashchromatography (silica gel) to afford the title compound.

Reference： [1]Synlett,2018,vol. 29,p. 650 - 654

77
7-bromo-1-(4-morpholin-yl)isoquinoline [ No CAS ]
[ 659742-21-9 ]
1-(4-morpholin-yl)-7-(6-methylpyridin-3-yl)-isoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With bis-triphenylphosphine-palladium(II) chloride; caesium carbonate; In 1,4-dioxane; ethanol; for 0.5h;Microwave irradiation; Sealed tube; Heating;	General procedure: 7-Bromo-1-(4-morpholinyl)isoqinoline (0.5 mmol), Cs2CO3 (0.5 mmol), phenylboronic acid (0.6 mmol), Pd (PPh3)2Cl2 (1 mol %), and 1,4-dioxane: ethanol= 4:1 (5 ml) were added to 10 mL vial. The vial was sealed with a crimp cap and placed in a Biotage initiator microwave cavity. After irradiation at 120 oC for 30 minutes and subsequent cooling, The reaction mixture was diluted with saturated aqueous ammonium chloride. Products were isolated by extraction into ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. Products were purified by silica gel column chromatography using a hexane: ethyl acetate =2:1. 1-(4-Morpholin-yl)-7-phenylisoquinoline (3a) was obtained with 82 % yields as a yellow solid. mp : 137-138; 1H NMR (300 MHz, CDCl3) delta 8.31 (s, 1H), 8.22 (d, J = 5.7 Hz, 1H), 7.89 (s, 2H), 7.79 (s, 4H), 7.70 (s, 1H), 7.34 (d, J = 5.7 Hz, 1H), 4.01 (m, 4H), 3.46 (m, 4H); 13C NMR (75 MHz, CDCl3) delta 161.4, 140.8, 139.1, 137.3, 129.4, 129.1, 127.8, 127.7, 127.3, 123.3, 121.9, 116.0, 67.1, 52.0, MS(m/z) : 290.37 (M+1). The compounds (3b-3t) were prepared general procedure for microwave promoted palladium-catalyzed aryl coupling reaction.

Reference： [1]Bulletin of the Korean Chemical Society,2018,vol. 39,p. 1259 - 1265

78
C₁₃H₁₃BrN₂ [ No CAS ]
[ 659742-21-9 ]
7-(6-methylpyridin-3-yl)-1-(pyrrolidin-1-yl)isoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With bis-triphenylphosphine-palladium(II) chloride; caesium carbonate; In 1,4-dioxane; ethanol; for 0.5h;Microwave irradiation; Sealed tube; Heating;	General procedure: 7-Bromo-1-(4-morpholinyl)isoqinoline (0.5 mmol), Cs2CO3 (0.5 mmol), phenylboronic acid (0.6 mmol), Pd (PPh3)2Cl2 (1 mol %), and 1,4-dioxane: ethanol= 4:1 (5 ml) were added to 10 mL vial. The vial was sealed with a crimp cap and placed in a Biotage initiator microwave cavity. After irradiation at 120 oC for 30 minutes and subsequent cooling, The reaction mixture was diluted with saturated aqueous ammonium chloride. Products were isolated by extraction into ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. Products were purified by silica gel column chromatography using a hexane: ethyl acetate =2:1. 1-(4-Morpholin-yl)-7-phenylisoquinoline (3a) was obtained with 82 % yields as a yellow solid. mp : 137-138; 1H NMR (300 MHz, CDCl3) delta 8.31 (s, 1H), 8.22 (d, J = 5.7 Hz, 1H), 7.89 (s, 2H), 7.79 (s, 4H), 7.70 (s, 1H), 7.34 (d, J = 5.7 Hz, 1H), 4.01 (m, 4H), 3.46 (m, 4H); 13C NMR (75 MHz, CDCl3) delta 161.4, 140.8, 139.1, 137.3, 129.4, 129.1, 127.8, 127.7, 127.3, 123.3, 121.9, 116.0, 67.1, 52.0, MS(m/z) : 290.37 (M+1). The compounds (3b-3t) were prepared general procedure for microwave promoted palladium-catalyzed aryl coupling reaction.

Reference： [1]Bulletin of the Korean Chemical Society,2018,vol. 39,p. 1259 - 1265

79
[ 36798-09-1 ]
[ 659742-21-9 ]
5-[4-(benzyloxy)-5-methoxy-2-nitrophenyl]-2-methylpyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 85℃; for 36h;Inert atmosphere;	The title compound was prepared using the synthetic procedures described for Example 29 changing step 1 as follows:A mixture of 1-(benzyloxy)-4-bromo-2-methoxy-5-nitrobenzene (Reference 1; 500.00 mg;1.48 mmol; 1.00 eq.), 6-methyl-3-pyridinylboronic acid (222.74 mg; 1.63 mmol; 1.10 eq.), sodium carbonate (235.07 mg; 2.22 mmol; 1.50 eq.) and 1,1-Bis(diphenylphosphino)fenocene]dichloropalladium(II) (54.10 mg; 0.07 mmol; 0.05 eq.) in 1,4- dioxane (14.79 mL) and water (1.10 mL) was subjected to three cycles of evacuation/back-filling with argon then it was heated under an argon atmosphere to 85 C. After 36 h the mixture was cooled to ambient temperature and concentrated. The residue was taken up in EtOAc, washed with water and brine, dried over MgSO4, filtered and concentrated to obtain a dark oil. This material was absorbedonto a plug of silica gel and purified by column chromatography (24 G ISCO Gold) eluting with 0-70% EtOAc in heptane to provide 5-[4-(benzyloxy)-5-methoxy-2-nitrophenyl]-2-methylpyridine (219 mg; 42%).

Reference： [1]Patent: WO2018/226998,2018,A1 .Location in patent: Page/Page column 172

80
6-chloro-10-isobutoxy-3,4-dimethyl-7,12-dihydroindeno[2',1':4,5]pyrrolo[3,2-c]quinoline [ No CAS ]
[ 659742-21-9 ]
C₃₀H₂₉N₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 120℃; for 3h;Inert atmosphere;	General procedure: 6-Chloro-10-isobutoxy-3,4-dimethyl-7,12-dihydroindeno [2',1':4,5]pyrrolo[3,2-c]quinoline (IV) (0.10 g, 0.26 mmol) and boronic acid (0.28 mmol) were dissolved in N,N-dimethylformamide (10 cm3). 1M sodium carbonate solution (1.5 cm3, 0.39 mmol) and tetrakis-(triphenylphosphine)palladium (0) catalyst (4.8 mg, 0.004 mmol) were added and the reaction mixture was heated at 120 for 3 hr in an oil bath under nitrogen atmosphere. After completion of reaction, the reaction mass was filtered through selite-545 bed and washed with N,N-dimethylformamide. The organic phase was removed under reduced pressure.The residue obtained was diluted with ethyl acetate and washed with 1N NaOH solution to remove residual boronic acid. The organic phase was separated and washed with water followed by brine and dried over anhydrous sodium sulphate. The product obtained was purified by column chromatography to give (V).

Reference： [1]Indian Journal of Heterocyclic Chemistry,2014,vol. 23,p. 359 - 366

81
C₁₉H₁₈IN₅O₂ [ No CAS ]
[ 659742-21-9 ]
C₂₅H₂₄N₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 80℃; for 2h;Inert atmosphere;	[00388] To a solution of Example 56a (65 mg, 0.14 mmol) in Dioxane/H20 (2 mL/0.4 mL) were added Example 56b (37 mg, 0.27 mmol), Na2C03 (44 mg, 0.41 mmol) and Pd(dppf)Cl2 (10 mg, 0.014 mol). The mixture was stirred at 80C for 2 h under N2. The mixture wasfiltrated and the filtratewas concentrated under reduced pressure. The residue was purified by Prep-HPLC to givethe desired product Example 56 (15 mg, yield 25%) as a whitesolid. LCMS [M+l]+ = 441.0. NMR (400 MHz, DMSO- d6) delta 11.28 (s, 1H), 8.86 (s, 1H), 8.75 (d, J= 2.5 Hz, 1H), 8.21 (d, J= 2.5 Hz, 1H), 8.07 (t, J= 7.9 Hz, 1H), 7.97 (dd, J= 8.0, 2.5 Hz, 1H), 7.92 (dd, J= 8.6, 2.5 Hz, 1H), 7.87 (d, J= 8.1Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.34 (dd, J= 8.4, 6.5 Hz, 2H), 4.64-4.56 (m, 1H), 4.50 (d, J= 9.4 Hz, 1H), 4.20 (t, J= 9.8 Hz, 1H), 3.16 (t, J= 10.3 Hz, 1H), 2.50 (s, 3H), 2.18-2.08 (m, 1H), 1.85-1.73 (m, 2H), 1.53 (d, J= 6.8 Hz, 3H).

Reference： [1]Patent: WO2019/51265,2019,A1 .Location in patent: Paragraph 00388

82
C₁₈H₁₆BrN₅O₂ [ No CAS ]
[ 659742-21-9 ]
C₂₄H₂₂N₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 95℃; for 16h;Inert atmosphere;	[00429] To a mixture of Example 70j (21 mg, 0.05 mmol), Example 70k (30 mg, 0.22 mmol), and Na2C03 (50 mg, 0.47 mmol) in dioxane/H20 (1.0 mL, v/v =3/1) was added Pd(dppf)Cl2 (2 mg). Then the mixture was degassed by bubbling N2 through the solution for 2 min using a syringe needle. After that, the mixture was heated at 95C for 16 h. The mixture was concentrated and directly purified by prep- TLC (DCM/MeOH = 20/1) to give the desired product Example 70 (7.0 mg, yield 33%) as a white solid. LCMS [M+l]+ = 427.0. NMR (400 MHz, Chloroform-) delta 10.49 (s, 1H), 8.80 (d, J= 2.4 Hz, 1H), 8.22 (s, 1H), 8.17 (dd, J= 5.1, 3.1Hz, 2H), 8.11 (d, J= 7.7 Hz, 1H), 7.97 (d, J= 7.9 Hz, 1H), 7.94-7.89 (m, 1H), 7.76 (dd, J= 7.8, 2.1Hz, 1H), 7.58 (d, J= 7.9 Hz, 1H), 7.32 (d, J= 8.0 Hz, 1H), 4.77 (d, J= 7.2 Hz, 2H), 4.68 (s, 2H), 4.01-3.93 (m, 2H), 2.66 (s, 3H), 2.36 (d, J= 6.6 Hz, 2H). Example 71: General Procedure for synthesis of compound Example 71

Reference： [1]Patent: WO2019/51265,2019,A1 .Location in patent: Paragraph 00429; 00423

83
C₁₉H₁₈IN₅O₂ [ No CAS ]
[ 659742-21-9 ]
C₂₅H₂₄N₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 95℃; for 2h;Inert atmosphere;	[00491] To a solution of Example 88i (280 mg, 0.59 mmol), Example 88j (121 mg, 0.88 mmol) and Na2C03 (188 mg, 1.77 mmol) in dioxane (30 mL) and water (5 mL) was added Pd(dppf)Cl2 (43 mg, 0.059 mmol). The mixture was degassed with N2 three times, heated to 95C for 2 h. The mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was purified by prep- TLC (DCM/MeOH = 10/1) to give 90 mg crude product. Then EtOAc (5 mL) was added, and the mixture was slurried for 30 min at room temperature, and filtrated. The solid was washed by EtOAc (2 mL), and dried under reduced pressure to give the desired product Example 88 (72 mg, yield 27%) as a pale brown solid. (>99% ee). LCMS [M+l] + = 441.0. NMR (400 MHz, DMSO- delta 11.28 (s, 1H), 8.85 (s, 1H), 8.74 (d, J= 2.4 Hz, 1H), 8.20 (d, J= 2.6 Hz, 1H), 8.06 (t, J= 7.9 Hz, 1H), 7.97 (dd, J= 8.1, 2.5 Hz, 1H), 7.92 (dd, J= 8.6, 2.6 Hz, 1H), 7.86 (d, J= 8.1Hz, 1H), 7.80 (d, J= 7.6 Hz, 1H), 7.34 (t, J= 8.1Hz, 2H), 4.59 (s, 1H), 4.50 (d, J= 9.8 Hz, 1H), 4.19 (t, J= 9.8 Hz, 1H), 3.16 (t, J= 9.9 Hz, 1H), 2.49 (s, 3H), 2.12 (s, 1H), 1.77 (q, J= 14.4, 13.1Hz, 2H), 1.53 (d, J = 6.9 Hz, 3H).

Reference： [1]Patent: WO2019/51265,2019,A1 .Location in patent: Paragraph 00491; 00485

84
C₁₇H₁₄IN₅OS [ No CAS ]
[ 659742-21-9 ]
C₂₃H₂₀N₆OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere;	[00505] To a mixture of Example 91j (40 mg, 0.086 mmol), Example 91k (18 mg, 0.129 mmol), and Na2C03 (28 mg, 0.258 mmol) in dioxane/H20 (1.8 mL, v/v = 3/1) was added Pd(dppf)Cl2 (3 mg). Then the mixture was degassed by bubbling N2 through the solution for 2 min using a syringe needle. After that, the mixture was heated at 100C for 2.0 h. The mixture was concentrated and directly purified by prep-TLC (DCM/MeOH = 20/1) to give the desired product Example 91 (28 mg, yield76%) as a white solid. LCMS [M+l]+ = 429.0. NMR (400 MHz, Chloroform-) delta 8.71 (s, 1H), 8.47 (d, J= 2.4 Hz, 1H), 8.21 (d, J= 7.8 Hz, 1H), 8.14 (s, 1H), 7.84 (t, J= 7.9 Hz, 1H), 7.60-7.55 (m, 2H), 7.44 (dd, J= 8.2, 2.1Hz, 1H), 7.35 (d, J= 2.1Hz, 1H), 7.24 (s, 1H), 7.17 (d, J= 8.0 Hz, 1H), 3.17 (s, 2H), 2.57 (s, 3H), 2.09 (d, J= 9.0 Hz, 2H), 1.78 (m, 2H).

Reference： [1]Patent: WO2019/51265,2019,A1 .Location in patent: Paragraph 00505; 00498

85
C₁₉H₁₆IN₅O₂ [ No CAS ]
[ 659742-21-9 ]
C₂₅H₂₂N₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 95℃; for 3h;Inert atmosphere;	[00526] To a solution of Example 97m (50 mg, 0.1 mmol) in Dioxane/H20 (2 mL/1 mL) were added Example 97n (16 mg, 0.12 mmol), Na2C03 (34 mg, 0.32 mmol) and Pd(dppf)Cl2 (8 mg, 0.01 mmol). The mixture was stirred at 95C for 3 h under N2. The mixture was filtrated and the filtrate was concentrated under reduced pressure. The residue was purified by silica-gel chromatography (DCM/MeOH = 20/1) to obtained a brown solid (40 mg), which was slurried by EtO Ac/Me OH (v/v = 10/1) to give the desired product Example 97 (14 mg, yield 30%) as a gray solid. LCMS [M+l]+ = 439.0. 'H NMR (400 MHz, DMSO- 6) delta 11.26 (s, 1H), 8.76 (d, J= 2.4 Hz, 1H), 8.66 (s, 1H), 8.10 (s, 1H), 7.98 (dd, J= 8.0, 2.5 Hz, 2H), 7.89 (d, J= 8.6 Hz, 1H), 7.71 (d, J= 7.6 Hz, 2H), 7.34 (d, J= 8.1Hz, 1H), 7.27 (d, J= 8.6 Hz, 1H), 4.42 (s, lH), 4.16 (s, 1H), 3.46 (s, 1H), 2.52 (s, 13H), 2.18 (s, 2H), 1.54 (q, J= 8.6, 6.9 Hz, 2H), 1.24-1.05 (m, 1H).

Reference： [1]Patent: WO2019/51265,2019,A1 .Location in patent: Paragraph 00526; 00517

86
C₁₉H₁₈IN₅O₂ [ No CAS ]
[ 659742-21-9 ]
C₂₅H₂₄N₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 90℃; for 2.5h;Inert atmosphere;	[00542] To a solution of Example 104g (50 mg, 0.105 mmol), Example 104h (17.3 mg, 0.126 mmol) and Na2C03 (33 mg, 0.316 mmol) in dioxane/H20 (2.5 mL, v/v = 4/1) was added Pd(dppf)Cl2 (7.7 mg, 0.011 mmol) at room temperature under N2. The reaction mixture was heated to 90C for 2.5 h under N2. The reaction mixture was purified by prep-HPLC to afford the desired product Example 104 (11.5 mg, yield 25%) as a white solid. LCMS [M+l]+ = 441.0. NMR (400 MHz, DMSO- 6) delta 8.76-8.73 (m, 2H), 8.22 (s, 1H), 8.08-8.04 (t, 1H), 8.00-7.84 (m, 5H), 7.43-7.41 (d, J= 8.0 Hz, 1H), 7.35-7.33 (d, J= 8.0 Hz, 1H), 4.40-4.36 (d, 2H), 4.28-4.25 (t, lH), 4.02-3.97 (t, 1H), 2.43 (s, 3H), 2.05 (s, 1H), 1.14 (d, J = 8.0 Hz, 4H).

Reference： [1]Patent: WO2019/51265,2019,A1 .Location in patent: Paragraph 00542; 00538

87
[ 13958-98-0 ]
[ 659742-21-9 ]
6-methyl-2''-phenyl-[3,3':6',4''-terpyridine]-4'-carbonitrile [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 14882 - 14886
Angew. Chem.,2019,vol. 131,p. 15024 - 15028,5

88
[ 13958-98-0 ]
[ 659742-21-9 ]
6'-methyl-[3,3'-bipyridine]-4-carbonitrile [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 14882 - 14886
Angew. Chem.,2019,vol. 131,p. 15024 - 15028,5

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	659742-21-9	MDL No. :	MFCD06801736
Formula :	C₆H₈BNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MZUSCPDSQJSBSY-UHFFFAOYSA-N
M.W :	136.94	Pubchem ID :	2763081
Synonyms :

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	39.03
TPSA :	53.35 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.02 cm/s

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.16
Log Po/w (WLOGP) :	-0.93
Log Po/w (MLOGP) :	-1.02
Log Po/w (SILICOS-IT) :	-0.77
Consensus Log Po/w :	-0.51

[ CAS No. 659742-21-9 ] {[proInfo.proName]}

Quality Control of [ 659742-21-9 ]

Related Doc. of [ 659742-21-9 ]

Product Details of [ 659742-21-9 ]

Calculated chemistry of [ 659742-21-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 659742-21-9 ]

Application In Synthesis of [ 659742-21-9 ]

[ 659742-21-9 ] Synthesis Path-Upstream 1~5

[ 659742-21-9 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 659742-21-9 ]

Organoboron

Related Parent Nucleus of
[ 659742-21-9 ]

Pyridines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-1.17
Solubility :	9.3 mg/ml ; 0.0679 mol/l
Class :	Very soluble
Log S (Ali) :	-0.84
Solubility :	19.9 mg/ml ; 0.145 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.27
Solubility :	7.3 mg/ml ; 0.0533 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.81

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

Yield	Reaction Conditions	Operation in experiment
92%	With potassium acetate In acetonitrile at 160℃; for 0.333333 h; Microwave	The INFLATE (4. 6MMOL) was dissolved in acetonitrile (30MOL) and placed into A 5M . microwave vessel. To the solution was added 1. 5 EQ of bis (PINACOLATO) DIBORON (6. 9MMOL ; 1. 71 G). The mixture was stirred on A magnetic stir plate until dissolution. To the mixture was added KOAC (13. 8MMOL ; 1. 35g) and 98mg of [1,1'-bis (DIPHENYLPHOSPHINO)- FERROCENE] DICHLOROPALLADIUM (II) (0. 03MOIpercent). The reaction mixture was heated at 160°C for 2 X 600s. After completion (monitored by LC-MS), the acetonitrile was evaporated to give a black solid. The solid was dissolved in DMSO, ms and purified by HPLC to give the boronic acid (580mg, 92percent; 4. 2MMOL). MS: MH+= 138
92%	With potassium acetate In acetonitrile at 160℃; for 0.333333 h; Microwave	The INFLATE (4. 6MMOL) was dissolved in acetonitrile (30MOL) and placed into A 5M . microwave vessel. To the solution was added 1. 5 EQ of bis (PINACOLATO) DIBORON (6. 9MMOL ; 1. 71 G). The mixture was stirred on A magnetic stir plate until dissolution. To the mixture was added KOAC (13. 8MMOL ; 1. 35g) and 98mg of [1,1'-bis (DIPHENYLPHOSPHINO)- FERROCENE] DICHLOROPALLADIUM (II) (0. 03MOIpercent). The reaction mixture was heated at 160°C for 2 X 600s. After completion (monitored by LC-MS), the acetonitrile was evaporated to give a black solid. The solid was dissolved in DMSO, ms and purified by HPLC to give the boronic acid (580mg, 92percent; 4. 2MMOL). MS: MH+= 138

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
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.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
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