[ CAS No. 943153-22-8 ] {[proInfo.proName]}

Name: 943153-22-8|(5-Chloro-2-methoxypyridin-3-yl)boronic acid|98%
Brand: Ambeed
SKU: A134667
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2D 3D

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Quality Control of [ 943153-22-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 943153-22-8 ]

SDS Specification

Alternatived Products of [ 943153-22-8 ]

Product Details of [ 943153-22-8 ]

CAS No. :	943153-22-8	MDL No. :	MFCD04114579
Formula :	C₆H₇BClNO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BZJQXIUWWLFBJS-UHFFFAOYSA-N
M.W :	187.39	Pubchem ID :	44754881
Synonyms :

Calculated chemistry of [ 943153-22-8 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	45.56
TPSA :	62.58 Å²

Pharmacokinetics

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) :	-6.95 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.69
Log Po/w (WLOGP) :	-0.58
Log Po/w (MLOGP) :	-0.57
Log Po/w (SILICOS-IT) :	-0.55
Consensus Log Po/w :	-0.2

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.67
Solubility :	3.96 mg/ml ; 0.0212 mol/l
Class :	Very soluble
Log S (Ali) :	-1.58
Solubility :	4.91 mg/ml ; 0.0262 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.66
Solubility :	4.09 mg/ml ; 0.0218 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.23

Safety of [ 943153-22-8 ]

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:

Application In Synthesis of [ 943153-22-8 ]

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

Downstream synthetic route of [ 943153-22-8 ]

[ 943153-22-8 ] Synthesis Path-Downstream 1~23

1
[ 943153-22-8 ]
[ 24358-62-1 ]
[ 943153-26-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	palladium diacetate; In water; at 180.0℃; for 0.116667h;Irradiation;Product distribution / selectivity;	EXAMPLE 39 (R)-1-Methyl-3-trifluoromethyl-1H-pyrazole-4-sulfonic acid 1-[4-(5-chloro-2-methoxypyridin-3-yl)-phenyl]-ethyl}-amide Palladium Acetate (30 mg, 0.134 mmol) was added to a mixture of (5-chloro-2-methoxy)pyrid-3-yl-boronic acid (500 mg, 2.67 mmol) and (R)-1-(4-bromophenyl)ethylamine (266 mg, 1.33 mmol) in water (20 ml). This mixture was heated in the microwave oven at 180 C. for 7 min, diluted with methanol (200 ml) and added to a SCX column eluting with 2M ammonia in methanol. The solvent was evaporated to give (R)-1-[4-(5-chloro-2-methoxy-pyridin-3-yl)-phenyl]-ethylamine (395 mg, 1.50 mmol, 113.2%) as an oil.

Reference： [1]Patent: US2007/149577,2007,A1 .Location in patent: Page/Page column 14

2
[ 578729-21-2 ]
[ 943153-22-8 ]
[ 943153-26-2 ]

Yield	Reaction Conditions	Operation in experiment
		To a suspension of (R)-1-(4-bromophenyl)ethylamine (23.89 g, 0.101 mol) in tetrahydrofuran (200 ml) was added triethylamine (21 ml), 4-dimethylaminopyridine (1.5 g) and di-tert-butyldicarbonate (26.5 g, 0.121 mol). The solution was stirred overnight then diluted with diethyl ether and washed with 2M aqueous hydrogen chloride solution, 10% aqueous sodium carbonate solution and brine. The organic phase was dried over anhydrous sodium sulfate and the solution concentrated to low volume. Heptane was added and the resulting white solid filtered off and dried to give (R)-[1-(4-bromophenyl)-ethyl]-carbamic acid tert-butyl ester (17 g). To a solution of (R)-[1-(4-bromophenyl)-ethyl]-carbamic acid tert-butyl ester (2 g, 6.7 mmol) in toluene (40 ml) was added 5-chloro-2-methoxypyridine boronic acid (2.5 g, 13.3 mmol), 2M aqueous sodium carbonate solution (6.8 ml) and tetrakis(triphenylphosphine) palladium (0) (0.4 g). The solution was heated under reflux for 48 h then washed with water, brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue dissolved in dichloromethane (50 ml) and the solution cooled to 0 C. Trifluoroacetic acid (20 ml) was added and the solution stirred for 3 h then evaporated to a gum which was chromatographed on a SCX column eluting with methanol then ammonia/methanol. The solvent was removed and the residue flash chromatographed on silica eluting with 9:1 dichloromethane/methanol then 9:1 dichloromethane/methanol-ammonia. The solvent was evaporated to give (R)-1-[4-(5-chloro-2-methoxy-pyridin-3-yl)-phenyl]-ethylamine (1.37 g) as a gum

Reference： [1]Patent: US2007/149577,2007,A1 .Location in patent: Page/Page column 14

3
[ 943153-22-8 ]
[ 880158-60-1 ]
[ 943153-34-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 120.0℃; for 0.25h;Irradiation;	3,5-Dimethyl-isoxazole-4-sulfonic acid 4-(5-chloro-2-methoxy-pyridin-3-yl)-3-methoxy-benzylamide A mixture of 3-methoxy-4-hydroxybenzaldehyde (0.406 g, 2.67 mmol), N-phenyl-bis (trifluoromethane)sulfonimide) (0.953 g, 2.67 mmol) and potassium carbonate (0.74 g, 5.3 mmol) in tetrahydrofuran (4.0 ml) was heated in a microwave oven at 120 C. for 10 min. The mixture was partitioned between ethyl acetate and dilute aqueous sodium hydroxide solution. The organic phase was washed with water, dried over anhydrous sodium sulfate and the solvent evaporated to give the trifluoro-methanesulfonic acid 4-formyl-2-methoxy-phenyl ester. A mixture of trifluoro-methanesulfonic acid 4-formyl-2-methoxy-phenyl ester (1.00 g, 3.52 mmol), titanium tetraethoxide (1.61 g, 7.04 mmol) and 2-methyl-2-propanesulfinamide (0.94 g, 7.75 mmol) in tetrahydrofuran (10 ml) was heated under reflux for 2 h, and then stirred at ambient temperature overnight. Further titanium tetraethoxide (0.80 g, 3.52 mmol) was added and the mixture stirred at ambient temperature overnight. The mixture was cooled in ice and then added portionwise to a stirred mixture of sodium borohydride (0.53 g, 14.1 mmol) in tetrahydrofuran (10 ml) at -78 C. The solution was allowed to warm to ambient temperature, treated slowly with water (with cooling) and extracted with ethyl acetate. The combined organic extracts were washed brine, dried over anhydrous sodium sulfate and the solvent evaporated. The residue was dissolved in methanol (10 ml), and treated with 2M hydrogen chloride in diethyl ether solution (5 ml). After standing for 2 hours, the solvent was evaporated, the residue triturated with diethyl ether, and the solid filtered and dried to give trifluoro-methanesulfonic acid 4-aminomethyl-2-methoxy-phenyl ester hydrochloride. A stirred solution of trifluoro-methanesulfonic acid 4-aminomethyl-2-methoxy-phenyl ester hydrochloride (0.37 g, 1.29 mmol) and triethylamine (0.4 ml, 2.7 mmol) in dichloromethane (10 ml) was treated with di-tert-butyl dicarbonate (0.28 g, 1.29 mmol) and stirred at ambient temperature overnight. The solvent was evaporated and the residue partitioned between ethyl acetate and water. The organic phase was washed with water, dried over anhydrous sodium sulfate and the solvent evaporated to give trifluoro-methanesulfonic acid 4-(tert-butoxycarbonylamino-methyl)-2-methoxy-phenyl ester. A mixture of trifluoro-methanesulfonic acid 4-(tert-butoxycarbonylamino-methyl)-2-methoxy-phenyl ester (0.20 g, 0.52 mmol), <strong>[943153-22-8]5-chloro-2-methoxy-pyridine-3-boronic acid</strong> (0.19 g, 1.0 mmol), tetrakis(triphenylphosphine)palladium (0) (0.073 g, 0.06 mmol), 2M aqueous sodium carbonate solution (2 ml), toluene (1 ml) and ethanol (1 ml) was heated in a microwave oven at 120 C. for 15 min. The mixture was partitioned between ethyl acetate and dilute aqueous sodium hydroxide solution. The organic phase was dried over anhyrous sodium sulfate, the solvent evaporated and the residue flash chromatographed over silica gel eluting with 1:1 heptane/ethyl acetate eluant to give the [4-(5-chloro-2-methoxy-pyridin-3-yl)-3-methoxy-benzyl]-carbamic acid tert-butyl ester. A solution of [4-(5-chloro-2-methoxy-pyridin-3-yl)-3-methoxy-benzyl]-carbamic acid tert-butyl ester (0.15 g, 0.4 mmol) in dichloromethane (10 ml) was treated with trifluoromethylacetic acid (0.5 ml), stirred at ambient temperature overnight, and the solvent evaporated to give 4-(5-chloro-2-methoxy-pyridin-3-yl)-3-methoxy-benzylamine trifluoromethyl acetate. The title compound was prepared in a similar manner to 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid (5'-chloro-3,2'-dimethoxy-biphenyl-4-ylmethyl)-amide (Example 41) using 4-(5-chloro-2-methoxy-pyridin-3-yl)-3-methoxy-benzylamine trifluoromethyl acetate instead of (5'-chloro-3,2'-dimethoxy-biphenyl-4-yl)-methylamine and 3,5-dimethylisoxazole-4-sulfonyl chloride instead of 5-chloro-1,3-dimethyl-1h-pyrazole-4-sulfonyl chloride. MS (ESI) m/z: 438.1 [M+H]+.

Reference： [1]Patent: US2007/149577,2007,A1 .Location in patent: Page/Page column 15-16

4
[ 943153-22-8 ]
(R)-2-methyl-propane-2-sulfinic acid [1-(4-bromo-2-methoxy-phenyl)-ethyl]-amide [ No CAS ]
(R)-1-[4-(5-chloro-2-methoxy-pyridin-3-yl)-2-methoxy-phenyl]-ethylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		(R)-1-Methyl-3-trifluoromethyl-1H-pyrazole-4-sulfonic acid {1-[4-(5-chloro-2-methoxy-pyridin-3-yl)-2-methoxy-phenyl]-ethyl}-amide A mixture of 4-bromo-2-hydroxyacetophenone (0.460 g, 2.0 mmol), titanium tetraethoxide (1.0 g, 4.0 mmol) and (R)-2-methyl-2-propanesulfinamide (0.266 g, 2.2 mmol) in dichloromethane (3.0 ml) was heated in a microwave oven at 120 C. for 15 min. The mixture was cooled in ice and added to a stirred mixture of sodium borohydride (0.30 g, 8.0 mmol) in tetrahydrofuran (50 ml). This mixture was stirred for 1 h at ambient temperature, treated with brine (30 ml) and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and the solvent evaporated The residue was flash chromatographed on silica gel eluting with 3:1 heptane/ethyl acetate to give (R)-2-methyl-propane-2-sulfinic acid [1-(4-bromo-2-methoxy-phenyl)-ethyl]-amide. A mixture of (R)-2-methyl-propane-2-sulfinic acid [1-(4-bromo-2-methoxy-phenyl)-ethyl]-amide (0.130 g, 0.4 mmol), <strong>[943153-22-8]5-chloro-2-methoxy-pyridine-3-boronic acid</strong> (0.150 g, 0.8 mmol), tetrakis(triphenylphosphine)palladium (0) (0.025 g, 0.02 mmol), 2M aqueous sodium carbonate solution (2 ml), toluene (1 ml) and ethanol (1 ml) was heated in a microwave oven at 120 C. for 15 min. The mixture was partitioned between ethyl acetate and dilute aqueous sodium carbonate solution. The organic layer was dried over anhydrous sodium sulfate, the solvent evaporated and the residue dissolved in methanol. This solution was treated with 2M hydrogen chloride in diethyl ether solution. After standing for 2 hours, the mixture was poured onto an SCX column, washed with methanol and then eluted with 1M ammonia in methanol solution. The solvent was evaporated and the residue flash chromatographed on silica gel eluting with 98:2 ethyl acetate/2M ammonia in methanol to give (R)-1-[4-(5-chloro-2-methoxy-pyridin-3-yl)-2-methoxy-phenyl]-ethylamine. The title compound was prepared in a similar manner to 1-methyl-3-trifluoromethyl-1H-pyrazole-4-sulfonic acid [1-(3,5'-difluoro-2'-methoxy-biphenyl-4-yl)-ethyl]-amide (Example 30) using (R)-1-[4-(5-chloro-2-methoxy-pyridin-3-yl)-2-methoxy-phenyl]-ethylamine instead of 1-(3,5'-difluoro-2'-methoxy-biphenyl-4-yl)-ethylamine. MS (ESI) m/z: 505.0 [M+H]+.

Reference： [1]Patent: US2007/149577,2007,A1 .Location in patent: Page/Page column 14-15

5
[ 943153-22-8 ]
[ 943153-21-7 ]
[ 943153-23-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 120.0℃; for 0.25h;Irradiation;	1-Methyl-3-trifluoromethyl-1H-pyrazole-4-sulfonic acid 4-(5-chloro-2-methoxy-pyridin-3-yl)-3-trifluoromethoxy-benzylamide To 4-hydroxy-3-trifluoromethoxy-benzylaldehyde (1.0 g, 4.85 mmol) in dry pyridine (4 ml) at 0 C. was slowly added trifluoromethane sulfonic anhydride maintaining the reaction temperature at 0 C. The mixture was allowed to warm to ambient temperature and left to stir for 1 h. The reaction mixture was quenched with water (50 ml) and extracted with ethyl acetate. The combined extracts were washed with 2M hydrochloric acid, water and dried over anhydrous magnesium sulfate. The solvent was evaporated to give trifluoro-methanesulfonic acid-4-formyl-2-trifluoromethoxy-phenyl ester (1.3 g, 3.85 mmol) as a brown oil. (+/-)-Tert-butylsulfinamine (0.311 g, 2.57 mmol) and titanium tetraethoxide (1.07 g, 4.69 mmol) were added to a solution of trifluoro-methanesulfonicacid-4-formyl-2-trifluoromethoxy-phenylester (0.791 g, 2.34 mmol) in dry tetrahydrofuran (20 ml) and the mixture stirred under nitrogen atmosphere at ambient temperature for 18 h. The reaction mixture was slowly added to a suspension of sodium borohyride (0.356 g, 9.4 mmol) in tetrahydrofuran at -50 C. and then allowed to warm to ambient temperature and left to stir for 1 h. The mixture was quenched with brine (50 ml) and ethyl acetate (50 ml) added. This mixture was filtered through a bed of dicalite and washed with copious amounts of water and ethyl acetate. The filtrate was phase separated, the organic phase dried over anhydrous magnesium sulfate and the solvent evaporated. Methanol (5 ml) was added to the residue and the mixture was poured onto an SCX column, washed with methanol and then eluted with 3M ammonia in methanol solution. The solvent was evaporated and the residue dissolved in 3M hydrogen chloride in diethyl ether solution. The solvent was evaporated to give trifluoro-methanesulfonicacid-4-aminomethyl-2-trifluoromethoxy-phenyl ester hydrochloride (0.184 g, 0.49 mmol) as a colourless solid. Trifluoro-methanesulfonicacid-4-aminomethyl-2-trifluoromethoxy-phenyl ester hydrochloride (0.184 g, 0.49 mmol) was suspended in dry tetrahydrofuran (3 ml). Di-tert-butyldicarbonate (0.108 g, 0.495 mmol) and triethylamine (0.198 g, 1.96 mmol) were added and the mixture stirred at ambient temperature for 2 h. The solvent was evaporated and the residue partitioned between water (10 ml) and ethyl acetate (10 ml). The organics phase was dried over anhydrous magnesium sulfate and the solvent evaporated to give trifluoro-methanesulfonicacid-4-(tert-butoxycarbonylaminomethyl)-2-trifluoromethoxy-phenyl ester (0.176 g, 0.407 mmol) as pale yellow oil. A mixture of trifluoro-methanesulfonicacid-4-(tert-butoxycarbonylaminomethyl)-2-trifluoromethoxy-phenyl ester (0.176 g, 0.407 mmol), 5-chloro-2-methoxypyridine boronic acid (0.151 g, 0.805 mmol), toluene (1 ml), ethanol (1 ml), 2M aqueous sodium carbonate solution (2 ml) and tetrakis(triphenylphosphine) palladium (0) was heated in a microwave oven at 120 C. for 15 min. The reaction mixture was quenched with brine and extracted with ethyl acetate. The combined extracts were filtered through dicalite and the filtrate dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue chromatographed on silica gel eluting with 6:40% heptane/ethyl acetate to give [4-(5-chloro-2-methoxypyridin-3-yl)-3-trifluoromethoxy-benzyl]-carbamic acid-tert-butyl ester (0.0745 g, 0.172 mmol) as a colourless solid. [4-(5-Chloro-2-methoxypyridin-3-yl)-3-trifluoromethoxy-benzyl]-carbamic acid-tert-butyl ester (0.0745 g, 0.172 mmol) was dissolved in dichloromethane (1 ml). Trifluoroacetic acid (1.485 g, 13 mmol) added and the solution stirred for 2 h at ambient temperature. The solvent was evaporated, the residue dissolved in methanol and then poured onto an SCX column. The column was washed with methanol and then eluted with ammonia in methanol solution. The solvent was evaporated to give 4-(5-chloro-2-methoxypyridin-3-yl)-3-trifluoromethoxy-benzylamine (0.045 g, 0.136 mmol) as oil. 1-Methyl-3-trifluoromethyl-1H-pyrazole-4-sulfonyl chloride (0.0302 g, 0.122 mmol) and triethylamine (0.038 g, 0.384 mmol) were added to a solution of 4-(5-chloro-2-methoxypyridin-3-yl)-3-trifluoromethoxy-benzylamine(0.042 g, 0.128 mmol) in dry dichloromethane (1 ml) and the mixture stirred at ambient temperature for 18 h. The solvent was evaporated and the residue chromatographed on silica gel eluting with 4:6 heptane/ethyl acetate to give the title compound (0.039 g, 0.072 mmol) as a clear solid. MS (ESI) m/z: 545 [M+H]+.

Reference： [1]Patent: US2007/149577,2007,A1 .Location in patent: Page/Page column 13-14

6
[ 943153-22-8 ]
[ 1126423-11-7 ]
[ 1126423-23-1 ]

Yield	Reaction Conditions	Operation in experiment
64%	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; water; for 6h;Heating / reflux;	12B 12C; A 250 ml round-bottomed flask was charged with 12B (3.60 g, 10.49 mmol), 5-chloro- 2-rnethoxypyridine-3-boronic acid (2.0 g, 10.67 mmol), [1,1 '- bis(diphenylphosphino)ferrocene]dichloropalladium(?) complex with dichloromethane (1 :1) (0.87 g, 1.06 mmol), and DME (50 ml). To the stirring solution, a solution of sodium carbonate (10 ml of 1.5 M, 15.0 mmol) was added via a syringe. The reaction mixture was maintained at reflux for 6 hours before cooled to room temperature. After concentration, the <n="131"/>residue was taken up with ethyl acetate (200 ml), washed with water (100 ml), and dried over sodium sulfate. The solvent was removed by distillation under reduced pressure and the residue was purified by Combiflash chromatography on silica gel using 0-10 % ethyl acetate in hexanes as the solvent to provide the product 12C as a white solid (2.4 g, 64%). M.S. found for C19Hi9ClN2O3: 359.2 (M+H)+.
64%	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; water; for 6h;Heating / reflux;	Step 2:; A 250 ml round-bottomed flask was charged with HB (3.60 g, 10.49 mmol), <strong>[943153-22-8]5-chloro-2-methoxypyridine-3-boronic acid</strong> (2.0 g, 10.67 mmol), [1,1 '- bis(diphenylphosphino)ferrocene]dichloropalladium(?) complex with dichloromethane (1 :1) (0.87 g, 1.06 mmol), and DME (50 mL). To the stirring solution, a solution of sodium carbonate (10 ml of 1.5 M, 15.0 mmol) was added via a syringe. The reaction mixture was maintained at reflux for 6 hours before cooled to room temperature. After concentration, the resulting residue was taken up with ethyl acetate (200 mL), washed with water (100 mL), and dried over sodium sulfate. The solvent was removed by distillation under reduced pressure and the resulting residue was purified using Combiflash chromatography on silica gel using 0-10 % ethyl acetate in hexanes as the solvent to provide the product HC as a white solid (2.4 g, 64%). M.S. found for Ci9H19ClN2O3: 359.2 (M+H)+.

Reference： [1]Patent: WO2009/32123,2009,A2 .Location in patent: Page/Page column 129-130
[2]Patent: WO2009/32124,2009,A1 .Location in patent: Page/Page column 167

8
[ 943153-22-8 ]
[ 1374134-70-9 ]
(4S,5R)-3-[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylthio)pyrimidin-4-yl]methyl}-4-methyl-5-[3-(trifluoromethoxy)phenyl]-1,3-oxazolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In tetrahydrofuran; water; at 85.0℃; for 1h;Inert atmosphere;	iNTERMEDIATE 19 (4S,5R-3- F5-(5-Chloro-2-methoxynyridin-3-yl-2-(methylthionyrimidin-4-yl]methyH -4- methyl-5- 13 -(trifluoromethoxynhenyl1 -1.3 -oxazolidin-2-one(4S,5R)-3- { [5-Bromo-2-(methylthio)pyrimidin-4-yl]methyl} -4-methyl-5- [3- (trifluoromethoxy)phenyl]-1,3-oxazolidin-2-one (II?1TERMEDIATE 9, 345 mg, 0.72 1 mmol), 5- chloro-2-methoxypyridin-3-ylboronic acid (203 mg, 1.082 mmol) and K2C03 (299 mg, 2.164 mmol) were added to a round bottom flask, which was then evacuated and charged with nitrogen 3 times. THF (4 mL) and water (0.4 mL) were then added. After evacuating and charging againwith nitrogen, 1,1bis(ditertbutylphosphino)ferrocene palladium dichloride (47.0 mg, 0.072 mmol) was added and the reaction heated for 60 minutes at 85C. LCMS showed complete conversion to product. The reaction was diluted with 5 mL acetonitrile and filtered through a 1 g C18 cartridge, eluting with 15 mL acetonitrile until the filtrate was colorless. The filtrate was then concentrated. Silica gel chromatography using a 0-30% ethyl acetate/hexanes lineargradient followed by an isocratic hold of 30% ethyl acetate/hexanes gave the title compound as a colorless oil. LCMS (M+H)*: 541.2

Reference： [1]Patent: WO2013/165854,2013,A1 .Location in patent: Page/Page column 32

9
[ 943153-22-8 ]
[ 1374134-77-6 ]
(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[5-(5-chloro-2-methoxypyridin-3-yl)-2-(3-fluoroazetidin-1-yl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In tetrahydrofuran; water; at 120.0℃; for 0.5h;Inert atmosphere;	EXAMPLE 1 (4S,5R-5- [3 ,5-Bis(trifluoromethylhenyl] -3- [5-(5-chloro-2-methoxyyridin-3-yl-2-(3 - fluoroazetidin- 1 -yl)pyrimidin-4-yl]methyfl -4-methyl- 1,3 -oxazolidin-2-one (4S,5R)-5- [3 ,5-Bis(trifluoromethyl)phenyl] -3- { [5-bromo-2-(3 -fluoroazetidin- 1 -yl)pyrimidin-4- yl]methyl}-4-methyl-1,3-oxazolidin-2-one (II?1TERMEDIATE 14, 425 mg, 0.763 mmol), <strong>[943153-22-8]5-chloro-2-methoxypyridin-3-ylboronic acid</strong> (214 mg, 1.144 mmol), 1,1bis(ditert butylphosphino)ferrocene palladium dichloride (49.7 mg, 0.076 mmol) and K2C03 (316 mg, 2.28 8 mmol) were added to a reaction vial that was evacuated and charged with nitrogen three times. The solid reactants were then mixed with THF (4 mL) and water (400 jil), degassed and refilled with nitrogen, capped and heated for 30 minutes at 125C in a BIOTAGE microwavereactor, after which LCMS showed complete conversion to product. The reaction was diluted with 5 mL acetonitrile and filtered through a lg RP C,8 silica cartridge, eluting with 15 mL acetonitrile until filtrate was colorless. The filtrate was concentrated prior to RP Prep purification on a X-Bridge 30 x 300 mm RP column. The sample was loaded in 7: 3: 1 CH3CN/water/DMSO (5 mL) and eluted with a 10-100% acetonitrile/water (0.1% NH4OH)linear gradient over 20 minutes. The product of interest eluted in 80% portion of above gradient. Pure fractions (rich cut; impure discarded) were concentrated and lyophilized to give a white solid. LCMS (M+H)*: 619.1. ?HNMR(CDC13, 500 MHz): 8.24 (s, 1H) 8.16 (s, 1H) 7.93 (s, 1H) 7.77 (s, 2H) 7.53 (s, 1H) 5.73 (m, 1H) 5.57 (m, 0.5H) 5.46 (m, 0.5H), 4.70 (d, J17.4Hz, 1H), 4.48 (m, 4H), 4.06 (d, J=17.5 Hz, 1H), 3.97 (s, 3H), 0.78 (bs, 3H). Rotomers gave broad signals. SPA IC50: 38 nM

Reference： [1]Patent: WO2013/165854,2013,A1 .Location in patent: Page/Page column 57; 58

10
[ 943153-22-8 ]
[ 944317-70-8 ]
[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylthio)pyrimidin-4-yl]methanol [ No CAS ]