Diisopropylethylamine → N-(2-methyl-7-(4-ureidopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethoxy)benzamide

HRID 1409278Notes

Reaction equation

Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:25])[C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=2)[CH:3]=1.Cl.[NH:27]1[CH2:32][CH2:31][CH:30]([NH:33][C:34]([NH2:36])=[O:35])[CH2:29][CH2:28]1.C(N(CC)C(C)C)(C)C>CN(C=O)C.CS(C)=O.CO>[CH3:11][C:9]1[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:25])[C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[CH:3]=[C:2]([N:27]3[CH2:32][CH2:31][CH:30]([NH:33][C:34]([NH2:36])=[O:35])[CH2:29][CH2:28]3)[N:7]2[N:8]=1

Participants

Conditions

Temperature: 80 °C

Procedure

An orange solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethoxy)benzamide (14A, 69 mg, 0.186 mmol), 1-(piperidin-4-yl)urea hydrochloride (40 mg, 0.279 mmol), and N,N-diisopropylethylamine (72 mg, 0.558 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 (45-60% (1:1 MeOH/MeCN)/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (26.9 mg, 39%). 1H NMR (DMSO-d6) δ: 10.98 (s, 1H), 8.06-8.11 (m, 2H), 7.44 (d, J=7.8 Hz, 2H), 7.25 (s, 1H), 6.09 (s, 1H), 6.02 (d, J=8.1 Hz, 1H), 5.34 (br. s., 2H), 4.23 (d, J=12.1 Hz, 2H), 3.62 (br. s., 1H), 3.15 (t, J=10.7 Hz, 2H), 2.31 (s, 3H), 1.87 (d, J=11.1 Hz, 2H), 1.39-1.51 (m, 2H); ESI-MS: m/z 478.3 (M+H)+.

Workup

temperatureAfter cooling to room temperature
filtrationfiltered
custompurified by preparatory HPLC (45-60% (1:1 MeOH/MeCN)/H2O gradient+0.01% TFA)

Sources & evidence

ORD record: ord-0800cf413f9449a38994e0be9ffd63e3
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921358B2

Reaction notes

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