Synthesis
General procedure for the synthesis of 2-methyl-4-hydroxymethylpyridine from (2-chloro-6-methylpyridin-4-yl)methanol: In a variant of the method described above, 2-chloro-6-methylpyridine-4-carboxylic acid, palladium catalyst (0.20 g, 10 mol% loaded on carbon), ethyl acetate (45 mL) and triethylamine (2.8 mL, 20 mmol) were mixed. The reaction mixture was placed under a hydrogen atmosphere at 1 atmosphere for 21 hours. Subsequently, additional Pearlman catalyst (0.2 g) was added and the reaction continued to be stirred for 5 hours under a hydrogen atmosphere to achieve dechlorination. Upon completion of the reaction, the mixture was filtered through a diatomaceous earth pad and the filtrate was concentrated. Purification by column chromatography (eluent ratio 5:95 methanol:dichloromethane) afforded (2-methylpyridin-4-yl)methanol (1.48 g, 88% yield). The obtained (2-methylpyridin-4-yl)methanol can be used to prepare 2-amino-3-(2-methylpyridin-4-yl)propionitrile, and 1-methyl-1H-indol-2-one carboxylic acid ((1S,2R)-2-{[cyano -(2-methylpyridin-4-ylmethyl)-methyl]-carbamoyl}-cyclohexyl)amide obtained by the method described above (186 mg, yield 62%). Results of mass spectrometry analysis: m/z 444 (M+H).
