Phosgene → N-(1-methyl-1H-indazol-4-yl)-4-[4-(trifluoromethyl)-2-pyridinyl]-1-piperazinecarboxamide

HRID 586083Notes

Reaction equation

HRID 586083 reaction equation
[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([NH2:11])[C:5]=2[CH:4]=[N:3]1.[C:12](Cl)(Cl)=[O:13].C(NC(C)C)(C)C.[F:23][C:24]([F:38])([F:37])[C:25]1[CH:30]=[CH:29][N:28]=[C:27]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:26]=1>C1(C)C=CC=CC=1>[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([NH:11][C:12]([N:34]3[CH2:35][CH2:36][N:31]([C:27]4[CH:26]=[C:25]([C:24]([F:38])([F:23])[F:37])[CH:30]=[CH:29][N:28]=4)[CH2:32][CH2:33]3)=[O:13])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3]1

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 7912DiisopropylamineHCID 1538381H-Indazol-4-amine, 1-methyl-HCID 112184921-[4-(Trifluoromethyl)pyridin-2-yl]piperazine

Product 1

HCID 22337654N-(1-methyl-1H-indazol-4-yl)-4-[4-(trifluoromethyl)-2-pyridinyl]-1-piperazinecarboxamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1-Methyl-1H-indazol-4-amine (560 mg, 3.81 mmol) in toluene (20 mL) was treated with 20% phosgene solution (2.5 mL) and refluxed overnight. The mixture was allowed to cool to ambient temperature and was concentrated under reduced pressure. The residue was taken up in THF (20 mL) and treated with diisopropylamine (5 mL) and 1-[4-(trifluoromethyl)-2-pyridinyl]piperazine (450 mg, 1.95 mmol). The mixture was refluxed overnight, allowed to cool to ambient temperature, and concentrated under reduced pressure. The residue was purified by flash chromatography (97:3 CH2Cl2:CH3OH to 95:5 CH2Cl2:CH3OH) to provide the title compound. The corresponding hydrochloride salt was prepared by treatment with methanolic HCl. 1H NMR (300 MHz, d6-DMSO) δ 8.78 (s, 1H), 8.44 (m, 1H), 8.07 (d, J=1.0 Hz, 1H), 7.83 (m, 1H), 7.19-7.31 (m, 3H), 7.02 (d, 9.2 Hz, 1H), 4.00 (s, 3H), 3.74 (m, 4H), 3.63 (m, 4H); MS (ESI+) m/z 405 (M+H)+.

Workup

  1. temperaturerefluxed overnight
  2. concentrationwas concentrated under reduced pressure
  3. temperatureThe mixture was refluxed overnight
  4. temperatureto cool to ambient temperature
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (97:3 CH2Cl2:CH3OH to 95:5 CH2Cl2:CH3OH)

Sources & evidence

ORD record
ord-df41d33ce34b487e88b7b55d84e7c2f8
Source dataset
uspto-grants-2005_08
Patent number
US06933311B2

Reaction notes

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