Trifluoroacetic acid → N-[1-(4-chlorophenyl)-5-isopropyl-pyrazol-4-yl]-3-methyl-1-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine-5-carboxamide

HRID 1754376Notes

Reaction equation

HRID 1754376 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH:13]([CH3:15])[CH3:14])=[C:11]([NH:16][C:17]([CH:19]3[N:24]4[C:25]([CH3:32])=[N:26][C:27]([C:28]([F:31])([F:30])[F:29])=[C:23]4[CH:22]=[CH:21][CH2:20]3)=[O:18])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>Cl.O=[Pt]=O.CCO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([CH:13]([CH3:15])[CH3:14])=[C:11]([NH:16][C:17]([CH:19]3[N:24]4[C:25]([CH3:32])=[N:26][C:27]([C:28]([F:31])([F:29])[F:30])=[C:23]4[CH2:22][CH2:21][CH2:20]3)=[O:18])[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86724380N-[1-(4-chlorophenyl)-5-isopropylpyrazol-4-yl]-3-methyl-1-(trifluoromethyl)-5,6-dihydroimidazo[1,5-a]pyridine-5-carboxamide

Product 1

HCID 76903148N-[1-(4-chlorophenyl)-5-isopropyl-pyrazol-4-yl]-3-methyl-1-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine-5-carboxamideYield 27%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 345198Adams' catalystCatalystHCID 702EthanolSolvent

Procedure

To N-[1-(4-chlorophenyl)-5-isopropylpyrazol-4-yl]-3-methyl-1-(trifluoromethyl)-5,6-dihydroimidazo[1,5-a]pyridine-5-carboxamide (30 mg, 0.064 mmol) was added EtOH (10 mL), 12 N HCl (4 drops), and PtO2 (30 mg). The resulting suspension was evacuated with hydrogen gas twice and stirred under hydrogen gas (55 psi) on Parr shaker for 25 min. the reaction mixture was then filtered through a syringe filter, concentrated in vacuo, and purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give N-[1-(4-chlorophenyl)-5-isopropyl-pyrazol-4-yl]-3-methyl-1-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine-5-carboxamide (10 mg, 0.0172 mmol, 27% yield) as a TFA salt. 1H NMR (400 MHz, Methanol-d4) δ 7.62 (s, 1H), 7.57 (d, J=11.76 Hz, 2H), 7.42 (d, J=11.76 Hz, 2H), 5.20-5.22 (m, 1H), 3.0-3.18 (m, 2H), 2.8-2.95 (m, 1H), 2.40 (s, 3H), 2.32-2.55 (m, 2H), 1.80-2.05 (m, 2H), 1.27 (d, J=23.4 Hz, 3H), 1.24 (d, J=23.4 Hz, 3H); MS: (ES) m/z calculated for C22H23ClF3N5O [M+H]+ 466.9, found 466.1.

Workup

  1. customThe resulting suspension was evacuated with hydrogen gas twice
  2. filtrationwas then filtered through a syringe
  3. filtrationfilter
  4. concentrationconcentrated in vacuo
  5. custompurified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-ab8cf3e49687459787e4d6a95bf6c08b
Source dataset
uspto-grants-2015_10
Patent number
US09169248B2

Reaction notes

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