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

HRID 470824Notes

Reaction equation

HRID 470824 reaction equation
N1C=CN=C1.[CH3:6][C:7]([Si:10](Cl)([CH3:12])[CH3:11])([CH3:9])[CH3:8].[Si:14]([O:21][CH2:22][C:23]1[CH:49]=[CH:48][C:26]([C:27]([NH:29][NH:30][C:31](=[O:47])[C@H:32]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]#[N:44])=[C:39]([Cl:45])[C:38]=2[CH3:46])[C@@H:33]([OH:35])[CH3:34])=[O:28])=[CH:25][CH:24]=1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].O>CN(C=O)C>[Si:10]([O:35][C@@H:33]([CH3:34])[C@@H:32]([NH:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]#[N:44])=[C:39]([Cl:45])[C:38]=1[CH3:46])[C:31]([NH:30][NH:29][C:27](=[O:28])[C:26]1[CH:48]=[CH:49][C:23]([CH2:22][O:21][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:15])[CH3:16])=[CH:24][CH:25]=1)=[O:47])([C:7]([CH3:9])([CH3:8])[CH3:6])([CH3:12])[CH3:11]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 670065934-((tert-butyldimethylsilyloxy)methyl)-N'-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)benzohydrazide

Product 1

HCID 67006201N'-((2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-((tert-butyldimethylsilyloxy)methyl)benzohydrazideYield 135%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Imidazole (3.99 g, 58.55 mol) and TBDMS-Cl (5.29 g, 35 mmol) were added sequentially to a pre-cooled (0° C.) solution of 4-((tert-butyldimethylsilyloxy)methyl)-N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)benzohydrazide (6.22 g, 11.71 mmol) in DMF (300 mL). The reaction mixture was allowed to warm to room temperature and stirred for 18 h, whereupon the solution was poured into H2O (120 mL). The white precipitate was filtered, washed with H2O (30 mL) and taken up in CH2Cl2 (200 mL). This organic layer was washed with brine (1×100 mL), dried (Na2SO4), filtered and concentrated to provide the title compound (10.2 g). This crude product was used directly in the next step.

Workup

  1. filtrationThe white precipitate was filtered
  2. washwashed with H2O (30 mL)
  3. washThis organic layer was washed with brine (1×100 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-7c4b67ff0a4040eca9794276ec1a9af7
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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