Triethylamine → 3-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxamide

Participants

Reaction Steps

A solution of 3-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxylic acid (Isomer 1) (170 mg, 0.49 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (187 mg, 0.584 mmol), and triethylamine (0.136 mL, 0.973 mmol) in DMF (5.0 mL) was stirred for 10 minutes, after which time ammonium hydroxide (0.20 mL, 1.46 mmol) was added. The reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was diluted with ethyl acetate (100 mL) and water (10 mL). The organic layer was separated and washed with water (2×10 mL) followed by brine (10 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to afford the crude product residue. The crude product residue was dissolved in a mixture of methanol (6 mL) and dichloromethane (20 mL). The mixture was diluted by the dropwise addition of hexanes (50 mL). The resulting suspension was stirred for 4 hours. The suspension was filtered and the collected solids were washed with hexanes/dichloromethane (1:1, 3×10 mL) followed by neat hexanes (2×10 mL). The collected solids were dried under reduced pressure to afford 3-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxamide (Isomer 1) MS ESI calcd. for C19H21N6O [M+H]+ 349. found 349. 1H NMR (500 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.46 (d, J=4.5 Hz, 2H), 8.15 (s, 1H), 7.78 (s, 1H), 7.72 (s, 1H), 7.40 (s, 1H), 7.37 (s, 1H), 6.98 (s, 1H), 6.88 (s, 1H), 6.81 (t, J=5.0 Hz, 1H), 5.03-4.96 (m, 1H), 3.05-2.98 (m, 1H), 2.69-2.61 (m, 2H), 2.57-2.51 (m, 2H), 2.27 (s, 3H).

Provenance & Evidence