Methyl 3-mercaptopropionate → Methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-(4-(2-(5-Bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone (40.0 g, 84.5 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (2.44 g, 4.22 mmol), Pd2dba3 (1.93 g, 2.11 mmol), methyl 3-mercaptopropanoate (18.7 mL, 169 mmol), N-ethyl-N-isopropylpropan-2-amine (15.4 mL, 88.7 mmol), and dioxane (250 mL) was heated to 95° C. under nitrogen for 2 hours. The reaction was cooled to ambient temperature and the resultant solids were filtered through celite washing with CH2Cl2. The filtrate was concentrated to a yellow oil and purified on silica eluting with 3%-5% MeOH/EtOAc to afford methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate as a yellow oil.

Provenance & Evidence