Guanidine → 4-[2-(4-Fluorophenyl)-6-trifluoromethylpyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine

HRID 1374720Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:20]([C:21](=O)[CH:22]=[CH:23]N(C)C)=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.Cl.[NH2:29][C:30]([NH2:32])=[NH2+:31].[O-]CC.[Na+].NC(N)=N>CCO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:20]([C:21]3[CH:22]=[CH:23][N:29]=[C:30]([NH2:32])[N:31]=3)=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:17])([F:19])[F:18])=[CH:15][N:10]3[N:9]=2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 2-(4-fluorophenyl)-3-(3-(dimethylamino)-2-propenoyl)-6-trifluoromethylpyrazolo[1,5-a]pyridine (100 mg, 0.27 mmol), guanidinium hydrochloride (52 mg, 0.54 mmol), and sodium ethoxide (73 mg, 1.08 mmol) in EtOH (4 mL) was stirred at reflux for 21 h. Additional guanidine was added in portions to the mixture until starting material was consumed as evidenced by TLC. The reaction mixture was cooled to 0° C. and the resulting precipitate was collected by filtration washed with cold EtOH and dried under vacuum to afford the title compound as a tan solid, 93 mg (92%). 1H NMR (acetone-d6) δ 9.19 (s, 1H), 8.73 (d, 1H, J=9.4 Hz), 8.13 (d, 1H, J=5.2 Hz), 7.78 (m, 2H), 7.63 (d, 1H, J=9.5 Hz), 7.34 (m, 2H), 6.41 (d, 1H, J=5.2 Hz), 6.17 (s, 1H). MS (+ve ion electrospray) 374 (100), (MH+).

Workup

temperatureat reflux for 21 h
customwas consumed
filtrationthe resulting precipitate was collected by filtration
washwashed with cold EtOH
customdried under vacuum

Sources & evidence

ORD record: ord-bcb0d4162a4d48469f85de7f3c01c210
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07166597B2

Reaction notes

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