(Piperidin-4-yl)urea hydrochloride → 2-(4-fluorophenyl)-N-(2-methyl-7-(4-ureidopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclopropanecarboxamide

Participants

Reaction Steps

The title compound was prepared by combining N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-(4-fluorophenyl)cyclopropanecarboxamide (13B, 0.15 g, 0.435 mmol), Et3NH (0.121 ml, 0.870 mmol), and the 1-(piperidin-4-yl)urea hydrochloride (0.156 g, 0.870 mmol) in NMP (1.450 ml) and heating the mixture 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 45-50% HPLC ([1:1 MeCN/MeOH]/H2O+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a tan solid (85 mg, 43%). 1H NMR (DMSO-d6) δ: 10.95 (s, 1H), 7.19-7.31 (m, 3H), 7.07-7.18 (m, 3H), 6.08 (s, 2H), 4.26 (d, J=12.6 Hz, 2H), 3.66 (br. s., 1H), 3.17 (t, J=11.7 Hz, 2H), 2.41-2.49 (m, 1H), 2.35 (s, 3H), 2.24-2.31 (m, 1H), 1.90 (br. s., 2H), 1.74-1.82 (m, OH), 1.43-1.57 (m, 3H), 1.35-1.43 (m, 1H), 1.32 (ddd, J=8.3, 6.6, 4.3 Hz, 0H); ESI-MS: m/z 452.3 (M+H)+. It was noted that rotamers were present.

Provenance & Evidence