Methyl 3-mercaptopropionate → HCID 66995289, compound

Participants

Reaction Conditions

Reaction Steps

A 1 L flask was charged with tert-butyl 4-(5-(5-bromo-3-phenoxypyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidine-1-carboxylate (Example 4, Step D, 24.4 g, 45.8 mmol), N-ethyl-N-isopropylpropan-2-amine (16.0 mL, 91.7 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (1.33 g, 2.29 mmol), and dioxane (450 mL). Nitrogen was bubbled through the solution for 30 minutes. Methyl 3-mercaptopropanoate (5.46 mL, 50.4 mmol) and Pd2dba3 (1.05 g, 1.15 mmol) were added and the reaction was heated at 95° C. overnight. The reaction was cooled to ambient temperature and the resultant solids were filtered through celite. The filtrate was concentrated and purified on silica (30 to 40% EtOAc in hexanes) to afford tert-butyl 4-(5-(5-(3-methoxy-3-oxopropylthio)-3-phenoxypyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidine-1-carboxylate (18.1 g, 69.1% yield) as a white foam.

Provenance & Evidence