N,N-Dimethylglycine → 1-(4-{(2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(5-imidazol-1-yl-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidin-1-yl}-5-chloro-pyrimidin-2-yl)-piperidin-4-ol

Participants

Reaction Steps

A 15 ml round-bottom tube is charged with 1-(4-{(2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidin-1-yl}-5-chloro-pyrimidin-2-yl)-piperidin-4-ol (32 mg, 0.044 mmol), imidazole (6 mg, 0.088 mmol), CuI (9 mg, 0.044 mmol), K2CO3 (12 mg, 0.088 mmol), N,N-dimethyl glycine (5 mg, 0.044 mmol) and DMSO (0.5 ml). Then the tube is sealed and heated to 110 degree for 18 hours. After cooling to rt, saturated NH3/H2O, EtOAc is added and then filtered through Celite pad. The solution is extracted with EtOAc and organic layer was dried over MgSO4. Removal of solvent and purification with reverse phase column give 1-(4-{(2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(5-imidazol-1-yl-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidin-1-yl}-5-chloro-pyrimidin-2-yl)-piperidin-4-ol (6.5 mg, 0.009 mmol, 20%).

Provenance & Evidence