Sodium hydride → 4-benzyloxycarbonyl-1-[3-(benzhydrylidene-amino)-4-cyano-benzyl]-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-one

HRID 1433058Notes

Reaction equation

HRID 1433058 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][C:13](=[O:17])[C@@H:12]1[CH2:18][CH2:19][S:20][CH3:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:24](=[N:37][C:38]1[CH:45]=[C:44]([CH2:46]Br)[CH:43]=[CH:42][C:39]=1[C:40]#[N:41])([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C.C([O-])(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:46][C:44]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[C:38]([N:37]=[C:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:45]=2)[C:13](=[O:17])[C@@H:12]1[CH2:18][CH2:19][S:20][CH3:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 179851902-(Benzhydrylideneamino)-4-bromomethylbenzonitrileHCID 670141654-Benzyloxycarbonyl-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-one

Product 1

HCID 865925564-benzyloxycarbonyl-1-[3-(benzhydrylidene-amino)-4-cyano-benzyl]-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-oneYield 80%

Reagents, catalysts & solvents 2

HCID 175AcetateSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-benzyloxycarbonyl-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-one (1.15 g, 3.74 mmol) in 10 ml of DMF is added at 0° C. sodium hydride (164 mg at 60% in oil, 4.12 mmol). The solution is stirred 10 minutes then 2-(benzhydrylidene-amino)-4-bromomethyl-benzonitrile (2.6 g at 52%, 3.74 mmol) in 25 ml of DMF is added dropwise. The resulting mixture is stirred for 20 hours at room temperature, diluted with ethyle acetate, washed with water, with a saturated aqueous NaHCO3 solution, brine. The solution is dried over MgSO4, concentrated. The resulting crude product is purified by column chromatography on silica gel eluting with 2% MeOH:CH2Cl2. The title compound (1.8 g, 80% yield) is obtained as a viscous oil.

Workup

  1. stirringThe resulting mixture is stirred for 20 hours at room temperature
  2. washwashed with water, with a saturated aqueous NaHCO3 solution, brine
  3. dry with materialThe solution is dried over MgSO4
  4. concentrationconcentrated
  5. customThe resulting crude product is purified by column chromatography on silica gel eluting with 2% MeOH

Sources & evidence

ORD record
ord-75b33e8dea9148acab46c57be5d0ab9c
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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