2-[4-Chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]butanoic acid → 2-(4-chloro-5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-1-(1-(4-fluorophenyl)-6,7-dihydro-1H-pyrazolo[4,3-b]pyridin-4(5H)-yl)butan-1-one

HRID 710631Notes

Reaction equation

HRID 710631 reaction equation
[Cl:1][C:2]1[C:3]([C:14]([F:17])([F:16])[F:15])=[N:4][N:5]([CH:8]([CH2:12][CH3:13])[C:9]([OH:11])=O)[C:6]=1[CH3:7].[F:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:33]3[CH2:32][CH2:31][CH2:30][NH:29][C:28]=3[CH:27]=[N:26]2)=[CH:21][CH:20]=1>>[Cl:1][C:2]1[C:3]([C:14]([F:17])([F:16])[F:15])=[N:4][N:5]([CH:8]([CH2:12][CH3:13])[C:9]([N:29]2[CH2:30][CH2:31][CH2:32][C:33]3[N:25]([C:22]4[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=4)[N:26]=[CH:27][C:28]2=3)=[O:11])[C:6]=1[CH3:7]

Participants

3

Reactant 2

HCID 669114582-[4-Chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]butanoic acidHCID 679846101-(4-fluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridine

Product 1

HCID 733355392-(4-chloro-5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-1-(1-(4-fluorophenyl)-6,7-dihydro-1H-pyrazolo[4,3-b]pyridin-4(5H)-yl)butan-1-oneYield 69%

Procedure

The title compound was prepared from 2-(4-chloro-5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)butanoic acid and 1-(4-fluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridine using General Method B. The product mixture was washed with 2×1 M NaHSO4. The reaction slurry was purified by flash chromatography (SiO2, 24 g column, eluting with 5-50% EtOAc in hexanes) to provide 81 mg (69%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H), 7.44 (m, 2H), 7.16 (m, 2H), 5.30 (dd, J=6.7, 8.6 Hz, 1H), 3.81 (ddd, J=3.2, 8.6, 11.5 Hz, 1H), 3.50 (ddd, J=3.1, 7.4, 10.2 Hz, 1H), 2.79 (dt, J=2.8, 6.3 Hz, 2H), 2.33 (m, 1H), 2.30 (s, 3H), 2.22 (m, 1H), 1.96 (m, 1H), 1.86 (m, 1H), 0.98 (t, J=7.0 Hz, 3H); MS: (ES) m/z calculated for C20H19ClF4N5O [M+H]+ 470.1, found 470.1.

Workup

  1. washThe product mixture was washed with 2×1 M NaHSO4
  2. customThe reaction slurry was purified by flash chromatography (SiO2, 24 g column, eluting with 5-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-22949eed4e314e08869ae986726edbb6
Source dataset
uspto-grants-2015_11
Patent number
US09181241B2

Reaction notes

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