PROCESS FOR PREPARING (5-(3-CHLOROPHENYL)-3-HYDROXYPYRIDINE-2-CARBONYL)-AMINOACETIC ACID FROM 5-((3-CHLOROPHENYL)-3-CHLORO-PYRIDIN-2-YL)-NITRILE, AND PROCESS FOR PREPARING 5-((HALOPHENYL)-3-HALO-PYRIDIN-2-YL)-NITRILE DERIVATIVES

摘要

A process for preparing compound (5):comprising:A. reacting (3-chlorophenyl)boronic acid:with 3,5-dichloro-2-cyanopyridine:in the presence of [1,1'-bis (diphenylphosphino)ferrocene]dichloro palladium(II) and K2 CO3 in DMF at 45C° to form 5-(3-chlorophenyl)-3 -chloro-2-cyanopyridine:B. reacting 5-(3-chlorophenyl)-3-chloro-2-cyanopyridine with sodium methoxide in methanol at reflux to form 5-(3-chlorophenyl)-3-methoxy-2-cyanopyridine:C. reacting 5-(3-chlorophenyl)-3-methoxy-2-cyanopyridine with 48% hydrobromic acid at reflux to form 5-(3-chlorophenyl)-3-hydroxypyridine-2-carboxylic acid:D. reacting 5-(3-chlorophenyl)-3-hydroxypyridine-2-carboxylic acid with glycine methyl ester:in the presence of CDI and DIPEA in DMSO at room temperature to form methyl {[5-(3-chlorophenyl)-3-hydroxypyridin-2-yl]amino}acetate:E. reacting methyl {[5-(3-chlorophenyl)-3-hydroxypyridin-2-yl]amino}acetate with sodium hydroxide in THF to form compound (5):