Cyanoacetic acid → N-(4-(2-(2-cyanoacetamido)pyridin-4-yloxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (150 mg, 0.34 mmol) (as prepared in Example 9) and 2-cyanoacetic acid (44 mg, 0.51 mmol) in DMF (2 mL) was added HATU (258 mg, 0.68 mmol) and DIEA (130 mg, 1 mmol) and the mixture was stirred at 60° C. under nitrogen overnight. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL) and H2O (50 mL) and the organic layer was washed with brine, dried and concentrated under reduced pressure. The residue was purified by prep-TLC to give N-(4-(2-(2-cyanoacetamido)pyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (70 mg, yield 64.5%). 1H-NMR (400 MHz, DMSO-d6): δ 10.99 (s, 1H), 10.94 (s, 1H), 9.81 (s, 1H), 8.23 (d, J=5.6 Hz, 1H), 8.08 (dd, J=12.4, 6.8 Hz, 1H), 7.59-7.55 (m, 4H), 7.15 (t, J=8.8 Hz, 2H), 6.80 (dd, J=6.0, 2.4 Hz, 1H), 3.92 (s, 2H), 1.61-1.56 (m, 4H); MS (ESI): m/z 510.2 [M+H]+.

Provenance & Evidence