Diisopropylethylamine → N-(7-(4-acetamidopiperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethoxy)benzamide

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Reaction Conditions

Reaction Steps

An orange solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethoxy)benzamide (14A, 69 mg, 0.186 mmol), N-(piperidin-4-yl)acetamide hydrochloride (40 mg, 0.279 mmol), and N,N-diisopropylethylamine (96 mg, 0.745 mmol) in DMF (1.8 mL) was stirred at 100° C. for 2 h, cooled to 80° C., and stirred overnight. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, filtered, and then purified by preparatory HPLC (50-70% (1:1 MeOH/MeCN)/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (31.3 mg, 35%). 1H NMR (DMSO-d6) δ: 10.99 (s, 1H), 8.05-8.12 (m, 2H), 7.85 (d, J=7.6 Hz, 1H), 7.44 (dd, J=9.1, 1.0 Hz, 2H), 7.26 (s, 1H), 6.09 (d, J=0.5 Hz, 1H), 4.28 (d, J=12.4 Hz, 2H), 3.72-3.94 (m, 1H), 3.14 (t, J=11.0 Hz, 2H), 2.31 (s, 3H), 1.84 (dd, J=13.1, 3.0 Hz, 2H), 1.75 (s, 3H), 1.41-1.58 (m, 2H); ESI-MS: m/z 477.3 (M+H)+.

Provenance & Evidence