Imidazole → HCID 67006212, compound

HRID 2388463Notes

Reaction equation

HRID 2388463 reaction equation
[C:1]([C:3]1[CH:31]=[CH:30][C:6]([C:7]([NH:9][NH:10][C:11](=[O:29])[C@H:12]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19]([C:25]([F:28])([F:27])[F:26])[CH:18]=2)[C@H:13]([OH:15])[CH3:14])=[O:8])=[CH:5][CH:4]=1)#[N:2].N1C=CN=C1.[CH3:37][C:38]([Si:41](Cl)([CH3:43])[CH3:42])([CH3:40])[CH3:39]>CN(C=O)C>[Si:41]([O:15][C@H:13]([CH3:14])[C@@H:12]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19]([C:25]([F:28])([F:27])[F:26])[CH:18]=1)[C:11]([NH:10][NH:9][C:7](=[O:8])[C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:31][CH:30]=1)=[O:29])([C:38]([CH3:40])([CH3:39])[CH3:37])([CH3:43])[CH3:42]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 67006794HCID 67006794, compound

Product 1

HCID 67006212HCID 67006212, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a pre-cooled (0° C.) solution of 4-cyano-N′-((2R,3R)-2-(4-cyano-3-(trifluoromethyl)phenylamino)-3-hydroxybutanoyl)benzohydrazide (1.57 g, 3.64 mmol) in DMF (100 mL) was added imidazole (1.98 g, 29.4 mmol) then TBSCl (2.20 g, 14.58 mmol). The reaction was warmed slowly to room temperature, stirred for 19 h, cooled to 0° C. and quenched with H2O (300 mL). The solution was extracted with EtOAc (250 mL). The organic extract was washed with H2O (2×100 mL) and 5% aq. citric acid (3×80 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a brown oil, which was purified by flash chromatography over silica gel (20-30% EtOAc in hexanes) to provide the title compound as a colourless solid (1.57 g, 79%): 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.06 (dm, J=8.6 Hz, 2H), 7.91 (dm, J=8.6 Hz, 2H), 7.73 (d, J=8.8 Hz, 1H), 7.36 (d, J=2.2 Hz, 1H), 7.14 (dd, J=2.4, 8.6 Hz, 1H), 6.52 (d, J=7.6 Hz, 1H), 4.49-4.39 (m, 2H), 1.36 (d, J=6.1 Hz, 3H), 0.85 (s, 9H), 0.12 (s, 3H), 0.09 (s, 3H).

Workup

  1. temperaturecooled to 0° C.
  2. customquenched with H2O (300 mL)
  3. extractionThe solution was extracted with EtOAc (250 mL)
  4. extractionThe organic extract
  5. washwas washed with H2O (2×100 mL) and 5% aq. citric acid (3×80 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide a brown oil, which
  10. customwas purified by flash chromatography over silica gel (20-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0c783e62e920435f85c5eb437fc6753f
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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