Imidazole → N'-((2R,3R)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-nitrobenzohydrazide

HRID 470870Notes

Reaction equation

HRID 470870 reaction equation
[Cl:1][C:2]1[C:3]([CH3:30])=[C:4]([NH:10][C@H:11]([C@H:27]([OH:29])[CH3:28])[C:12]([NH:14][NH:15][C:16](=[O:26])[C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].N1C=CN=C1.[CH3:36][C:37]([Si:40](Cl)([CH3:42])[CH3:41])([CH3:39])[CH3:38]>CN(C=O)C>[Si:40]([O:29][C@H:27]([CH3:28])[C@@H:11]([NH:10][C:4]1[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=1[CH3:30])[C:12]([NH:14][NH:15][C:16](=[O:26])[C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=1)=[O:13])([C:37]([CH3:39])([CH3:38])[CH3:36])([CH3:42])[CH3:41]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 67006072N'-((2R,3R)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-nitrobenzohydrazide

Product 1

HCID 59193039N'-((2R,3R)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-nitrobenzohydrazideYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a pre-cooled (0° C.) solution of N′-((2R,3R)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-nitrobenzohydrazide (12.0 g, 27.79 mmol) in DMF (650 mL) was added imidazole (15.13 g, 222.31 mmol) then TBSCl (16.75 g, 111.15 mmol). The reaction was warmed slowly to room temperature, stirred for 72 h, cooled to 0° C. and quenched with H2O (600 mL). The solution was extracted with EtOAc (700 mL). The organic extract was washed with H2O (2×300 mL) and 5% aq. citric acid (3×250 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a light yellow oil, which was purified by flash chromatography over silica gel (30-40% EtOAc in hexanes) to provide the title compound as a colourless solid (8.50 g, 56%): 1H NMR (400 MHz, d6-DMSO, δ in ppm) 10.93 (s, 1H), 10.57 (s, 1H), 8.34 (dm, J=8.8 Hz, 2H), 8.07 (dm, J=9.0 Hz, 2H), 7.59 (d, J=8.6 Hz, 1H), 6.84 (d, J=9.0 Hz, 1H), 5.69 (d, J=8.4 Hz, 1H), 5.28 (s, 1H), 4.38 (pentet, J=6.3 Hz, 1H), 4.16 (dd, J=6.5, 8.0 Hz, 1H), 2.26 (s, 3H), 1.27 (d, J=6.3 Hz, 3H), 0.85 (s, 9H), 0.08 (s, 3H), 0.05 (s, 3H).

Workup

  1. temperaturecooled to 0° C.
  2. customquenched with H2O (600 mL)
  3. extractionThe solution was extracted with EtOAc (700 mL)
  4. extractionThe organic extract
  5. washwas washed with H2O (2×300 mL) and 5% aq. citric acid (3×250 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide a light yellow oil, which
  10. customwas purified by flash chromatography over silica gel (30-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-dd0aa9dd00f44c34ad1630d8cb881d75
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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