Imidazole → HCID 67006087, compound

HRID 1254756Notes

Reaction equation

HRID 1254756 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-e5268a0d69a648ff84bd2f46e35e91bf
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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