Methyl 3-mercaptopropionate → Tert-butyl 4-(2-(5-(3-methoxy-3-oxopropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate

Participants

Reaction Steps

A 100 mL round-bottomed flask was charged with tert-butyl 4-(2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate (1.6 g, 3.0 mmol), N-ethyl-N-isopropylpropan-2-amine (1.0 mL, 6.0 mmol), Xantphos (0.087 g, 0.15 mmol), and Dioxane (25 mL). Nitrogen was bubbled through the solution for 10 minutes. Methyl 3-mercaptopropanoate (0.40 mL, 3.6 mmol) and Pd2dba3 (0.068 g, 0.075 mmol) were added and the reaction was plunged into a 95° C. oil bath for 6 hours. The reaction was cooled to room temperature and the solids filtered through celite and concentrated. The residue was purified on silica (30% EtOAc in hexanes) to afford tert-butyl 4-(2-(5-(3-methoxy-3-oxopropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate (1.4 g; 81.48% yield) as a white foam.

Provenance & Evidence