Phosgene → HCID 22337674, compound

HRID 586082Notes

Reaction equation

HRID 586082 reaction equation
[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH2:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:13](Cl)(Cl)=[O:14].C(NC(C)C)(C)C.[CH3:24][N:25]1[C:33]2[CH:32]=[CH:31][CH:30]=[C:29]([NH2:34])[C:28]=2[CH:27]=[N:26]1>C1(C)C=CC=CC=1>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([CH2:9][NH:10][C:13]([NH:34][C:29]2[CH:30]=[CH:31][CH:32]=[C:33]3[C:28]=2[CH:27]=[N:26][N:25]3[CH3:24])=[O:14])=[CH:11][CH:12]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 7912DiisopropylamineHCID 1538381H-Indazol-4-amine, 1-methyl-HCID 27356554-tert-Butylbenzylamine

Product 1

HCID 22337674HCID 22337674, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

4-tert-Butylbenzylamine (0.46 mL, 2.62 mmol) in toluene (8 mL) was treated with 20% phosgene solution (1.4 mL) and refluxed for 3 hours. The mixture was allowed to cool to ambient temperature and concentrated under reduced pressure. The residue was then taken up in toluene (10 mL) and treated with diisopropylamine (3 mL) and 1-methyl-1H-indazol-4-amine (prepared as described in J. Med. Chem. 45:742 (2002); 200 mg, 1.36 mmol). The reaction mixture was heated at 80° C. for 3 hours, allowed to cool to ambient temperature, and concentrated under reduced pressure. The residue was purified by flash chromatography (98:2 CH2C12:CH3OH to 95:5 CH2Cl2:CH3OH, eluant gradient) to provide the title compound. The corresponding hydrochloride salt was prepared with methanolic HCl. 1H NMR (300 MHz, d6-DMSO) δ 8.72 (s, 1H), 8.03 (d, J=0.7 Hz, 1H), 7.66 (dd, J=7.8 Hz, 0.6 Hz, 1H), 7.37 (m, 2H), 7.27 (m, 2H), 7.24 (m, 1H), 7.13 (m, 1H), 6.74 (m, 1H), 4.30 (d, J=5.8 Hz, 2H), 3.99 (s, 3H), 1.27 (s, 9H); MS (ESI+) m/z 337 (M+H)+.

Workup

  1. temperaturerefluxed for 3 hours
  2. concentrationconcentrated under reduced pressure
  3. temperatureThe reaction mixture was heated at 80° C. for 3 hours
  4. temperatureto cool to ambient temperature
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (98:2 CH2C12:CH3OH to 95:5 CH2Cl2:CH3OH, eluant gradient)

Sources & evidence

ORD record
ord-c28725acc70e4603b2b4d2452d1d5a58
Source dataset
uspto-grants-2005_08
Patent number
US06933311B2

Reaction notes

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