Methyl iodide → HCID 68511681、化合物

反応式

[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH:14]3[CH:18]([OH:19])[CH2:17][N:16]([C:20]([C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=4)=[O:21])[CH2:15]3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:33]I>CN1C(=O)CCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:9][CH2:10][N:11]([CH:14]3[CH:18]([O:19][CH3:33])[CH2:17][N:16]([C:20]([C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=4)=[O:21])[CH2:15]3)[CH2:12][CH2:13]2)=[O:7])=[CH:29][CH:30]=1

参加物

反応条件

温度: 4 °C

実験手順

To a cold (3-5° C.) solution of starting material {3-[4-(4-Chloro-benzoyl)-piperazin-1-yl]-4-hydroxy-pyrrolidin-1-yl}-(4-chloro-phenyl)-methanone in 1 mL of NMP was added NaH (4 mg, 0.17 mmol). The mixture was then stirred at 3-5° C. for 15 mins. MeI (7.5 uL) was then added. After 2 hours, the reaction was quenched by adding 50 μL AcOH. The mixture was then partitioned in EtOAc and 1M K2CO3. The separated organic phase was washed with brine, dried over Na2SO4 and concentrated down to dryness. The resulting crude residue was purified by column chromatography on silica (Methanol 1 CH2Cl2: 0%-10%). The pure product was converted to it HCl salt by precipitation in a mixture of ethanol\ether and conc. HCl, to give 43 mg of salt of {3-[4-(4-Chloro-benzoyl)-piperazin-1-yl]-4-methoxy-pyrrolidin-1-yl}-(4-chloro-phenyl)-methanone as a white solid.