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

HRID 563302

Reaction equation

HRID 563302 reaction equation
[Cl:1][C:2]1[C:3]([CH3:28])=[C:4]([NH:10][C@H:11]([C@@H:25]([OH:27])[CH3:26])[C:12]([NH:14][NH:15][C:16](=[O:24])[C:17]2[CH:22]=[CH:21][C:20]([I:23])=[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:27][C@@H:25]([CH3:26])[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[CH3:28])[C:12]([NH:14][NH:15][C:16](=[O:24])[C:17]1[CH:22]=[CH:21][C:20]([I:23])=[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 67006188N'-((2R,3S)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-iodobenzohydrazide

Product 1

HCID 67005875N'-((2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-iodobenzohydrazideYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-iodobenzohydrazide (7.3 g, 14.2 mmol) in DMF (60 mL) were added imidazole (3.9 g, 57.3 mmol) and TBSCl (4.3 g, 28.5 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 (8.6 g, 97%), 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-29487b23e7254871b765dd8e4b0e5781
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Linked notes

Loading…