Imidazole → N'-((2R,3R)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyanophenylamino)butanoyl)-4-cyanobenzohydrazide

HRID 1254719Notes

Reaction equation

HRID 1254719 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([C@H:26]([OH:28])[CH3:27])[C:12]([NH:14][NH:15][C:16](=[O:25])[C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].N1C=CN=C1.[CH3:34][C:35]([Si:38](Cl)([CH3:40])[CH3:39])([CH3:37])[CH3:36]>CN(C=O)C>[Si:38]([O:28][C@H:26]([CH3:27])[C@@H:11]([NH:10][C:4]1[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[CH:3]=1)[C:12]([NH:14][NH:15][C:16](=[O:25])[C:17]1[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=1)=[O:13])([C:35]([CH3:37])([CH3:36])[CH3:34])([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 67006229N'-((2R,3R)-2-(3-Chloro-4-cyanophenylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide

Product 1

HCID 67006638N'-((2R,3R)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyanophenylamino)butanoyl)-4-cyanobenzohydrazideYield 98.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a pre-cooled (0° C.) solution of N′-((2R,3R)-2-(3-chloro-4-cyanophenylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide (1.65 g, 4.15 mmol) in DMF (100 mL) was added imidazole (2.26 g, 33.4 mmol) then TBSCl (2.50 g, 16.60 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 (10-30% EtOAc in hexanes) to provide the title compound as a colourless amorphous solid (2.09 g, 98%): 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.06 (dm, J=8.6 Hz, 2H), 7.92 (dm, J=8.6 Hz, 2H), 7.53 (d, J=8.8 Hz, 1H), 7.04 (d, J=2.2 Hz, 1H), 6.91 (dd, J=2.4, 8.8 Hz, 1H), 6.26 (d, J=7.6 Hz, 1H), 4.42 (pentet, J=5.5 Hz, 1H), 4.31 (dd, J=5.5, 7.8 Hz, 1H), 1.35 (d, J=6.3 Hz, 3H), 0.87 (s, 9H), 0.12 (s, 3H), 0.10 (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 (10-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-211d783731174ede89cf636e03eac28a
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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