Synthesis
a) To a methanolic solution of 3-bromo-2-pyridinecarboxylic acid (1 g, 4.9 mmol), a few drops of concentrated sulfuric acid were slowly added as a catalyst at room temperature. The reaction mixture was stirred at room temperature for 12 hours to ensure complete reaction. Upon completion of the reaction, methanol was removed by rotary evaporation to give the crude product. The crude product was purified by a CombiFlash fast chromatography system on a silica gel column with the eluent being a hexane solution of 20-50% ethyl acetate, resulting in methyl 3-bromopyridinecarboxylate (450 mg, 41% yield). Subsequently, compound 17 (82% yield) was synthesized in a series of reaction steps according to the method described in Example 1 using methyl 3-bromopyridinecarboxylate as starting material, and compound 4 was finally prepared.
References
[1] Patent: US2011/136833, 2011, A1. Location in patent: Page/Page column 27
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 2, p. 635 - 654
[3] Patent: US3963733, 1976, A
