Carbon Tetrachloride → tert-Butyl(R)-4-(5-(isoquinolin-6-yl)-1,3,4-oxadiazol-2-yl)-1-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate

HRID 598902Notes

Reaction equation

HRID 598902 reaction equation
[C:1]([O:5][C:6](=[O:38])[NH:7][C@@H:8]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=1)[CH2:9][CH2:10][C:11]([NH:13][NH:14][C:15]([C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[CH:23]=[N:22][CH:21]=[CH:20]2)=O)=[O:12])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)Cl.CCN(C(C)C)C(C)C>C1COCC1>[CH:23]1[C:24]2[C:19](=[CH:18][C:17]([C:15]3[O:12][C:11]([CH2:10][CH2:9][C@@H:8]([NH:7][C:6](=[O:38])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:27][C:28]4[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:35])[F:36])=[CH:30][CH:29]=4)=[N:13][N:14]=3)=[CH:26][CH:25]=2)[CH:20]=[CH:21][N:22]=1

Participants

6

Reactant 4

HCID 5943Carbon TetrachlorideHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 57950611tert-Butyl((1R)-4-(2-(6-isoquinolinylcarbonyl)hydrazino)-4-oxo-1-(4-(trifluoromethyl)benzyl)butyl)carbamate

Product 1

HCID 57950648tert-Butyl(R)-4-(5-(isoquinolin-6-yl)-1,3,4-oxadiazol-2-yl)-1-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamateYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl((1R)-4-(2-(6-isoquinolinylcarbonyl)hydrazino)-4-oxo-1-(4-(trifluoromethyl)benzyl)butyl)carbamate (0.080 g, 0.15 mmol) and triphenylphosphine (0.070 mL, 0.30 mmol), and 0.5 mL CCl4 were heated under nitrogen in 10 mL THF at 50° C. for 20 hours. 0.2 mL DIEA was added, and the reaction mixture was heated at reflux 4 hours. The reaction mixture was filtered and the solid was washed with THF. The filtrate was diluted with EtOAc and washed with saturated aqueous sodium bicarbonate (3×). The solvent was evaporated, and the residue was purified by chromatography on silica gel (60% EtOAc in hexane) to provide the product as a white solid (0.06 g, 78%). LCMS (API-ES) m/z: 513 (M+H+).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux 4 hours
  3. filtrationThe reaction mixture was filtered
  4. washthe solid was washed with THF
  5. additionThe filtrate was diluted with EtOAc
  6. washwashed with saturated aqueous sodium bicarbonate (3×)
  7. customThe solvent was evaporated
  8. customthe residue was purified by chromatography on silica gel (60% EtOAc in hexane)

Sources & evidence

ORD record
ord-8eb01288580442eb92113d108e8de2eb
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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