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

HRID 563276Notes

Reaction equation

HRID 563276 reaction equation
N1C=CN=C1.[CH3:6][C:7]([Si:10](Cl)([CH3:12])[CH3:11])([CH3:9])[CH3:8].[Cl:14][C:15]1[CH:16]=[C:17]([NH:23][C@H:24]([C@@H:41]([OH:43])[CH3:42])[C:25]([NH:27][NH:28][C:29](=[O:40])[C:30]2[CH:35]=[CH:34][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:32][CH:31]=2)=[O:26])[CH:18]=[CH:19][C:20]=1[C:21]#[N:22].O>CN(C=O)C>[Si:10]([O:43][C@@H:41]([CH3:42])[C@@H:24]([NH:23][C:17]1[CH:18]=[CH:19][C:20]([C:21]#[N:22])=[C:15]([Cl:14])[CH:16]=1)[C:25]([NH:27][NH:28][C:29](=[O:40])[C:30]1[CH:35]=[CH:34][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:32][CH:31]=1)=[O:26])([C:7]([CH3:9])([CH3:8])[CH3:6])([CH3:12])[CH3:11]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 58433608N'-((2R,3S)-2-(3-Chloro-4-cyanophenylamino)-3-hydroxybutanoyl)-4-(methylsulfonyl)benzohydrazide

Product 1

HCID 58433612N'-((2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyanophenylamino)butanoyl)-4-(methylsulfonyl)benzohydrazideYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Imidazole (3.77 g, 55.44 mol) and TBDMS-Cl (5.01 g, 33.24 mmol) were added sequentially to a pre-cooled (0° C.) solution of N′-((2R,3S)-2-(3-chloro-4-cyanophenylamino)-3-hydroxybutanoyl)-4-(methylsulfonyl)benzohydrazide (5 g, 11.08 mmol) in DMF (350 mL). The reaction mixture was allowed to warm to room temperature and stirred for 17 h, whereupon the solution was poured into H2O (90 mL). The white precipitate was filtered, washed with H2O (30 mL) and taken up in CH2Cl2 (170 mL). This organic layer was washed with brine (1×50 mL), dried (Na2SO4), filtered and concentrated to provide the title compound (4.3 g, 69%). 1H NMR (400 MHz, acetone-d6, δ in ppm) 9.8 (br s, 1H), 8.08 (d, J=8.0 Hz, 2H), 8.04 (d, J=9 Hz, 2H), 7.53 (d, J=8 Hz, 1H), 6.99 (s, 1H), 6.85 (d, J=8 Hz, 1H), 6.22 (d, J=8 Hz, 1H), 4.43-4.38 (m, 1H), 4.27-4.22 (m, 1H), 1.37 (d, J=7 Hz, 3H), 0.86 (s, 9H), 0.11 (s, 3H) and 0.05 (s, 3H).

Workup

  1. filtrationThe white precipitate was filtered
  2. washwashed with H2O (30 mL)
  3. washThis organic layer was washed with brine (1×50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-6252022428fd4cca903f7e55d250bba4
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

Loading…