Ammonia → 5-Amino-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [5-(2-trifluoromethyl-phenyl)-isoxazol-4-yl]-amide

HRID 474361Notes

Reaction equation

[F:1][C:2]([F:28])([F:27])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[O:13][N:12]=[CH:11][C:10]=1[NH:14][C:15]([C:17]1[CH:18]=[N:19][N:20]2[CH:25]=[CH:24][C:23](Cl)=[N:22][C:21]=12)=[O:16].[NH3:29]>CC(O)C>[F:1][C:2]([F:28])([F:27])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[O:13][N:12]=[CH:11][C:10]=1[NH:14][C:15]([C:17]1[CH:18]=[N:19][N:20]2[CH:25]=[CH:24][C:23]([NH2:29])=[N:22][C:21]=12)=[O:16]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 5-chloro-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [5-(2-trifluoromethyl-phenyl)-isoxazol-4-yl]-amide (200 mg, 0.49 mmol, 1.0 equiv) and 2M ammonia in propan-2-ol (4 mL) was sealed and heated in a microwave reactor at 120° C. for 40 minutes. The solvent was removed under vacuum and the resultant residue was purified by flash column chromatography on silica gel (gradient: 0 to 5% methanol in dichloromethane) to afford 58.6 mg (31%) of 5-amino-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [5-(2-trifluoromethyl-phenyl)-isoxazol-4-yl]-amide. LCMS (ESI) m+H=389.1; 1H NMR (400 MHz, DMSO-d6) δ: 9.60 (s, 1H), 9.07 (s, 1H), 8.63 (d, 1H), 8.18 (s, 1H), 7.99 (d, 1H), 7.95-7.77 (m, 3H), 7.70-6.60 (br, 2H), 6.39 (d, 1H).

Workup

customwas sealed
customThe solvent was removed under vacuum
customthe resultant residue was purified by flash column chromatography on silica gel (gradient: 0 to 5% methanol in dichloromethane)

Sources & evidence

ORD record: ord-c74de83705d24b6986a48ec641bac3a0
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637526B2

Reaction notes

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