4-Methylmorpholine → (R)-N-(4-((2-(2-(benzyloxy)propanamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-2-benzyloxy-propionic acid (500 mg, 2.78 mmol) and N-methylmorpholine (416 mg, 4.16 mmol) in anhydrous CH2Cl2 was added isobutyl chloroformate (566 mg, 4.32 mmol) dropwise. The mixture was stirred at 25° C. for 1 h. N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (200 mg, 0.452 mmol) was added and the resulting mixture was stirred at 25° C. for 12 h. The reaction mixture was concentrated in vacuo to give (R)—N-(4-((2-(2-(benzyloxy)propanamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (200 mg, 71.5%). It was used without further purification.

Provenance & Evidence