Cesium carbonate → Altiratinib

Participants

Reaction Conditions

Reaction Steps

N-(4-(2-Chloropyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (0.25 g, 0.541 mmol) (as prepared in Example 1), cyclopropanecarboxamide (0.092 g, 1.083 mmol), xantphos (0.014 g, 0.024 mmol), and cesium carbonate (0.265 g, 0.812 mmol) were dissolved in dry dioxane (5.41 mL) and argon was bubbled through the mixture for 5 minutes. Pd2(dba)3 (7.44 mg, 0.00812 mmol) was added and additional argon was bubbled through the system. It was then fitted with a reflux condenser and a balloon of argon and heated at 100° C. for 20 hours. The reaction mixture was cooled to room temperature and then partitioned between water (40 mL) and ethyl acetate (70 mL). The layers were separated and the organic layer was washed with brine (50 mL), dried over magnesium sulfate, and evaporated to yield a peach-colored solid. It was stirred in dichloromethane (10 mL) and a cream-colored solid was collected by suction filtration and washed with additional dichloromethane to yield N-(4-(2-(cyclopropanecarboxamido)pyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (0.238 g, 86% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.00 (s, 1H), 10.89 (s, 1H), 9.79 (s, 1H), 8.20 (d, 1H), 8.07 (dd, 1H), 7.63 (d, 1H), 7.56 (m, 3H), 7.16 (m, 2H), 6.74 (dd, 1H), 1.95 (quintet, 1H), 1.62 (m, 2H), 1.56 (m, 2H), 0.75 (m, 4H); MS (ESI) m/z: 511.1 (m+H+).

Provenance & Evidence