Methyl iodide → 4-[3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carbonyl]-1-methyl-piperazin-2-one

HRID 416015

Reaction equation

HRID 416015 reaction equation
[CH:1]1([N:7]2[CH2:11][CH2:10][CH:9]([CH2:12][C:13]3[C:18]([Cl:19])=[CH:17][C:16]([C:20]4[CH:25]=[CH:24][C:23]([C:26]([N:28]5[CH2:33][CH2:32][N:31]6[CH2:34]CC[CH:30]6[CH2:29]5)=[O:27])=[CH:22][CH:21]=4)=[CH:15][C:14]=3[Cl:37])[C:8]2=[O:38])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].IC.CC(C)=[O:45].C(OCC)C>CN(C)C=O.C(OCC)(=O)C>[Cl:37][C:14]1[CH:15]=[C:16]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([N:28]3[CH2:33][CH2:32][N:31]([CH3:34])[C:30](=[O:45])[CH2:29]3)=[O:27])=[CH:22][CH:21]=2)[CH:17]=[C:18]([Cl:19])[C:13]=1[CH2:12][CH:9]1[CH2:10][CH2:11][N:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:8]1=[O:38]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 21584533Acetone diethyletherHCID 57741511Racemic 1-cyclohexyl-3-[3,5-dichloro-4'-(hexahydro-pyrrolo[1,2-a]pyrazine-2-carbonyl)-biphenyl-4-ylmethyl]-pyrrolidin-2-on

Product 1

HCID 577415714-[3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carbonyl]-1-methyl-piperazin-2-oneYield 32%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Treat a solution of racemic 1-cyclohexyl-3-[3,5-dichloro-4′-(hexahydro-pyrrolo[1,2-a]pyrazine-2-carbonyl)-biphenyl-4-ylmethyl]-pyrrolidin-2-on (0.245 g, 0.46 mmol) in dimethylformamide (6 mL) with 60% sodium hydride (0.037 g, 0.93 mmol) and stir for 15 minutes at room temperature under a nitrogen atmosphere. Cool the reaction to 0° C., treat with iodomethane (0.25 g, 1.76 mmol) and then stir at room temperature for 16 hours under a nitrogen atmosphere. Quench the reaction with 1N hydrochloric acid, dilute with ethyl acetate and wash with water. Dry the organic layer with sodium sulfate and purify by silica gel chromatography using a gradient of 0 to 10% methanol in dichloromethane to afford product. Re-crystallize from acetone/diethyl ether to afford 81 mg (32%) of the title compound: MS (m/z) 542 (M+).

Workup

  1. temperatureCool
  2. customthe reaction to 0° C.
  3. stirringstir at room temperature for 16 hours under a nitrogen atmosphere
  4. customQuench
  5. customthe reaction with 1N hydrochloric acid
  6. washwash with water
  7. dry with materialDry the organic layer with sodium sulfate
  8. custompurify by silica gel chromatography
  9. customto afford product

Sources & evidence

ORD record
ord-a152e68b21f74bb2913a78960c34c72e
Source dataset
uspto-grants-2012_01
Patent number
US08088776B2

Linked notes

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