4-(Trifluoromethylthio)benzoyl chloride → N-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethylthio)benzamide
Reaction equation
[CH3:1][C:2]1[CH:17]=[C:5]2[N:6]=[C:7]([NH2:16])[CH:8]=[C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[N:4]2[N:3]=1.[F:18][C:19]([F:31])([F:30])[S:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=1>N1C=CC=CC=1>[CH3:1][C:2]1[CH:17]=[C:5]2[N:6]=[C:7]([NH:16][C:25](=[O:26])[C:24]3[CH:28]=[CH:29][C:21]([S:20][C:19]([F:31])([F:18])[F:30])=[CH:22][CH:23]=3)[CH:8]=[C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[N:4]2[N:3]=1Participants
4
Procedure
A solution of 2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amine (10A, 62 mg, 0.276 mmol) and pyridine (0.69 mL) in a 20 mL scintillation vial was cooled to 0° C. then treated with 4-(trifluoromethylthio)benzoyl chloride (100 mg, 0.415 mmol). The reaction mixture was stirred for 2 h, partitioned between saturated aqueous sodium bicarbonate and ethyl acetate, and the organic layer subsequently washed with water and then brine. The organic layer was then dried over sodium sulfate, filtered, concentrated under reduced pressure, diluted with methanol, filtered, and purified via preparative HPLC (80-80% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (58.8 mg, 50%). Melting point (100.9-101.6° C.). 1H NMR (DMSO-d6) δ: 11.49 (s, 1H), 8.15 (d, J=8.6 Hz, 2H), 8.06 (dd, J=6.7, 2.9 Hz, 2H), 7.93 (s, 1H), 7.87 (d, J=8.3 Hz, 2H), 7.56-7.66 (m, 3H), 6.41 (s, 1H), 2.40 (s, 3H); ESI-MS: m/z 429.1 (M+H)+. Melting point (100.9-101.6° C.).