Dimethylformamide → 1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone

HRID 710620Notes

Reaction equation

Cl[CH2:2][C:3]([N:5]1[CH2:10][CH2:9][CH2:8][C:7]2[N:11]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[N:12]=[CH:13][C:6]1=2)=[O:4].CN(C=O)C.C([O-])([O-])=O.[K+].[K+].[CH3:32][C:33]1[NH:37][N:36]=[C:35]([C:38]([F:41])([F:40])[F:39])[CH:34]=1>C1COCC1>[F:20][C:17]1[CH:18]=[CH:19][C:14]([N:11]2[C:7]3[CH2:8][CH2:9][CH2:10][N:5]([C:3](=[O:4])[CH2:2][N:37]4[C:33]([CH3:32])=[CH:34][C:35]([C:38]([F:41])([F:40])[F:39])=[N:36]4)[C:6]=3[CH:13]=[N:12]2)=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 75 °C

Procedure

2-Chloro-1-(1-(4-fluorophenyl)-6,7-dihydro-1H-pyrazolo[4,3-b]pyridin-4(5H)-yl)ethanone (118 mg, 0.4 mmol) was diluted in 1.2 mL of 2:1 THF:DMF and treated with K2CO3 (111 mg, 0.8 mmol) and 5-methyl-3-(trifluoromethyl)-1H-pyrazole (60 mg, 0.4 mmol). The slurry was heated to 75° C. for 2 hours. The reaction slurry was purified by normal phase flash chromatography (24 g column, eluting with 10-80% EtOAc in hexanes) to provide 109 mg (67%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.36 (s, 0.8H), 7.59 (s, 0.2H), 7.42-7.47 (m, 2H), 7.12-7.25 (m, 2H), 5.25 (s, 0.4H), 5.14 (s, 1.6H), 3.92 (m, 0.4H), 3.86 (m, 1.6H), 2.86 (t, J=6.2 Hz, 2H), 2.37 (s, 2.4H), 2.36 (m, 0.6H), 2.11 (m, 1.6H), 2.04 (m, 0.4H); MS: (ES) m/z calculated for C19H18F4N5O [M+H]+ 408.1, found 408.1.

Workup

customThe reaction slurry was purified by normal phase flash chromatography (24 g column, eluting with 10-80% EtOAc in hexanes)

Sources & evidence

ORD record: ord-d7acb1a57f784aa48bdb708f029c10bf
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181241B2

Reaction notes

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