Imidazole → 4-Bromo-N'-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)benzohydrazide

HRID 470841Notes

Reaction equation

HRID 470841 reaction equation
[Br:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([NH:8][NH:9][C:10](=[O:26])[C@H:11]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[C:18]([Cl:24])[C:17]=2[CH3:25])[C@@H:12]([OH:14])[CH3:13])=[O:7])=[CH:4][CH:3]=1.N1C=CN=C1.[CH3:34][C:35]([Si:38](Cl)([CH3:40])[CH3:39])([CH3:37])[CH3:36]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([NH:8][NH:9][C:10](=[O:26])[C@H:11]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[C:18]([Cl:24])[C:17]=2[CH3:25])[C@@H:12]([O:14][Si:38]([C:35]([CH3:37])([CH3:36])[CH3:34])([CH3:40])[CH3:39])[CH3:13])=[O:7])=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 670068114-Bromo-N'-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)benzohydrazide

Product 1

HCID 670067824-Bromo-N'-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)benzohydrazideYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-bromo-N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)benzohydrazide (4.0 g, 8.6 mmol) in DMF (60 mL) were added imidazole (2.3 g, 33.8 mmol) and TBSCl (2.6 g, 17.2 mmol) at 0° C. After addition, the mixture was allowed to warm to room temperature gradually and stirred overnight. The reaction was quenched by adding ice-water and extracted with EtOAc. The EtOAc extracts were washed with water, brine and dried over Na2SO4. Removal of the solvent gave a residue, which was purified by SiO2 column to give the title compound (4.68 g, 94%), which was used directly in the next step.

Workup

  1. additionAfter addition
  2. customThe reaction was quenched
  3. additionby adding ice-water
  4. extractionextracted with EtOAc
  5. washThe EtOAc extracts were washed with water, brine
  6. dry with materialdried over Na2SO4
  7. customRemoval of the solvent
  8. customgave a residue, which
  9. customwas purified by SiO2 column

Sources & evidence

ORD record
ord-92e9781c44a54519a5ba49e239696b52
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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