Piperidine-3-carbonitrile → N-(7-(3-cyanopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

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A solution of N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 50 mg, 0.151 mmol) and piperidine-3-carbonitrile (33 mg, 0.302 mmol) in NMP (0.950 mL) was stirred at 85° C. overnight. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC, 35-60% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a orange solid (52 mg, 85%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.45 (s, 6 H) 1.73-2.11 (m, 4 H) 3.25-3.34 (m, 1 H) 3.53-3.63 (m, 1 H) 3.68-3.79 (m, 1 H) 3.98 (dd, J=12.51, 2.65 Hz, 1 H) 4.12-4.23 (m, 1 H) 6.38 (d, J=2.27 Hz, 1 H) 7.46 (s, 1 H) 7.60 (d, J=8.59 Hz, 2 H) 8.00 (d, J=8.59 Hz, 2 H) 8.12 (d, J=2.27 Hz, 1 H) 10.93 (s, 1 H). ESI-MS: m/z 405.3 (M+H)+.

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