Diisopropylethylamine → N-(4-(2-acetamidopyrimidin-4-yloxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of Example A3 (300 mg, 1.07 mmol) and 1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarboxylic acid (240 mg, 1.07 mmol) (as prepared in Example B1) in DMF (20 mL) was added HATU (440 mg, 3.2 mmol) and DIEA (280 mg, 2.1 mmol) in portions. The reaction mixture was stirred at 60° C. under nitrogen overnight. After cooling to room temperature water (30 mL) was added and the solution was extracted with ethyl acetate (3×50 mL). The combined organics were washed with brine (3×50 mL), dried over sodium sulfate, and concentrated. The crude product was purified by preparative HPLC to give N-(4-(2-acetamidopyrimidin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (42 mg, 8% yield) as a white solid. 1HNMR (300 MHz, DMSO-d6): δ 10.95 (s, 1H), 10.40 (s, 1H), 9.75 (s, 1H), 8.49-8.51 (d, J=5.7 Hz, 1H), 7.94-8.01 (dd, J=12.3 Hz, J=8.1 Hz, 1H), 7.48-7.60 (m, 3H), 7.05-7.16 (m, 2H), 6.83-6.84 (d, J=5.4 Hz, 1H), 1.92 (s, 3H), 1.53-1.59 (d, J=19.2 Hz, 4H).

Provenance & Evidence