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

HRID 416015

反応式

HRID 416015 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-a152e68b21f74bb2913a78960c34c72e
出典データセット
uspto-grants-2012_01
特許番号
US08088776B2

関連ノート

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