Chloroacetonitrile → {5-Chloro-2-[4-(2,6-dimethoxy-phenyl)-piperidine-1-carbonyl]-indol-1-yl}-acetonitrile

HRID 912756Notes

Reaction equation

HRID 912756 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]3[C:24]([O:25][CH3:26])=[CH:23][CH:22]=[CH:21][C:20]=3[O:27][CH3:28])[CH2:15][CH2:14]1)=[O:12])=[CH:5]2.[H-].[Na+].Cl[CH2:32][C:33]#[N:34]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:32][C:33]#[N:34])[C:6]([C:11]([N:13]1[CH2:14][CH2:15][CH:16]([C:19]3[C:24]([O:25][CH3:26])=[CH:23][CH:22]=[CH:21][C:20]=3[O:27][CH3:28])[CH2:17][CH2:18]1)=[O:12])=[CH:5]2

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 24758Sodium hydrideHCID 24989651(5-chloro-1H-indol-2-yl)-[4-(2,6-dimethoxy-phenyl)-piperidin-1-yl]-methanone

Product 1

HCID 24989653{5-Chloro-2-[4-(2,6-dimethoxy-phenyl)-piperidine-1-carbonyl]-indol-1-yl}-acetonitrileYield 20.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 40 mg (0.10 mmol) of (5-chloro-1H-indol-2-yl)-[4-(2,6-dimethoxy-phenyl)-piperidin-1-yl]-methanone in DMF (3 ml) at RT was added 5 mg (0.11 mmol) of NaH (in oil, 55%). After 20 minutes, 8 mg (0.10 mmol) of chloro-acetonitrile was added and stirring was continued over night. The reaction mixture was concentrated in vacuo and purification by preparative HPLC (30% CH3CN/H2O) afforded 9 mg (18%) of {5-chloro-2-[4-(2,6-dimethoxy-phenyl)-piperidine-1-carbonyl]-indol-1-yl}-acetonitrile as a white solid.

Workup

  1. waitwas continued over night
  2. concentrationThe reaction mixture was concentrated in vacuo and purification by preparative HPLC (30% CH3CN/H2O)

Sources & evidence

ORD record
ord-e7489ad6c9e04bda8591996571f3f220
Source dataset
uspto-grants-2011_09
Patent number
US08026259B2

Reaction notes

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