Imidazole → HCID 67006087, compound

HRID 2388509Notes

Reaction equation

HRID 2388509 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C@H:10]([C@H:27]([OH:29])[CH3:28])[C:11]([NH:13][NH:14][C:15](=[O:26])[C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)=[O:12])=[CH:5][C:4]=1[C:30]([F:33])([F:32])[F:31])#[N:2].N1C=CN=C1.[CH3:39][C:40]([Si:43](Cl)([CH3:45])[CH3:44])([CH3:42])[CH3:41]>CN(C=O)C>[Si:43]([O:29][C@H:27]([CH3:28])[C@@H:10]([NH:9][C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:30]([F:33])([F:32])[F:31])[CH:5]=1)[C:11]([NH:13][NH:14][C:15](=[O:26])[C:16]1[CH:17]=[CH:18][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][CH:21]=1)=[O:12])([C:40]([CH3:42])([CH3:41])[CH3:39])([CH3:45])[CH3:44]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 67006587HCID 67006587, compound

Product 1

HCID 67006087HCID 67006087, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a pre-cooled (0° C.) solution of N′-((2R,3R)-2-(4-cyano-3-(trifluoromethyl)phenylamino)-3-hydroxybutanoyl)-4-(methylsulfonyl)benzohydrazide (5.16 g, 10.7 mmol) in DMF (150 mL) was added imidazole (4.36 g, 64.0 mmol) then TBSCl (4.81 g, 32.0 mmol). The reaction was warmed slowly to room temperature, stirred for 17 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 brine (2×200 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a brown oil, which was purified by flash chromatography over silica gel (50% EtOAc in hexanes) to provide the title compound (5.29 g, 83%): 1H NMR (400 MHz, acetone-d6, δ in ppm) 10.06 (s, 2H), 8.10 (dm, J=8.6 Hz, 2H), 8.03 (dm, J=8.6 Hz, 2H), 7.70 (d, J=8.6 Hz, 1H), 7.35 (d, J=2.4 Hz, 1H), 7.14 (dd, J=2.4, 8.6 Hz, 1H), 6.57 (d, J=7.4 Hz, 1H), 4.50-4.41 (m, 2H), 3.17 (s, 3H), 1.36 (d, J=5.9 Hz, 3H), 0.85 (s, 9H), 0.11 (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 brine (2×200 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 (50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f8f49da0a2f549ef977fdf7d8607a632
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

Loading…