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【结 构 式】

【药物名称】MS-377

【化学名称】1-(4-Chlorophenyl)-3(R)-[4-(2-methoxyethyl)-1-piperazinylmethyl]pyrrolidin-2-one (-)-D-tartrate

【CA登记号】

【 分 子 式 】C22H32ClN3O8

【 分 子 量 】501.96864

【开发单位】Mitsui Pharmaceuticals (Originator)

【药理作用】Antipsychotic Drugs, PSYCHOPHARMACOLOGIC DRUGS, sigma Receptor Antagonists

合成路线1

Reaction of 4-chloroaniline (I) with gamma-butyrolactone (II) in a refluxing solution of HCl afforded pyrrolidinone (III). Subsequent carboxylation of (III) with diethyl carbonate in the presence of NaH gave ketoester (IV), which was reduced to alcohol (V) using calcium borohydride in MeOH. Further treatment of (V) with methanesulfonyl chloride and Et3N provided the corresponding mesylate (VI). Methoxyethylpiperazine (IX) was prepared by alkylation of formylpiperazine (VII) with 2-methoxyethyl bromide, followed by acid deprotection of the alkylated formylpiperazine (VIII). Then, condensation of mesylate (VI) with piperazine (IX) provided racemic (X). Finally, resolution with D-tartaric acid in EtOH yielded the target (R)-isomer.

1 Mita, N.; Nagase, H.; Iizuka, H.; Oguchi, T.; Sakai, K.; Horikomi, K.; Miwa, T.; Takahashi, S. (Mitsui Chemicals, Inc.); Pyrrolidinone derivs. and their use as antipsychotic medicaments. EP 0839805; JP 1998182602 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(II) 20576 dihydro-2(3H)-furanone 96-48-0 C4H6O2 详情 详情
(III) 27732 1-(4-chlorophenyl)-2-pyrrolidinone 7661-33-8 C10H10ClNO 详情 详情
(IV) 27733 ethyl 1-(4-chlorophenyl)-2-oxo-3-pyrrolidinecarboxylate C13H14ClNO3 详情 详情
(V) 27734 1-(4-chlorophenyl)-3-(hydroxymethyl)-2-pyrrolidinone C11H12ClNO2 详情 详情
(VI) 27735 [1-(4-chlorophenyl)-2-oxo-3-pyrrolidinyl]methyl methanesulfonate C12H14ClNO4S 详情 详情
(VII) 23801 1-piperazinecarbaldehyde; N-Formylpiperazine 7755-92-2 C5H10N2O 详情 详情
(VIII) 27736 4-(2-methoxyethyl)-1-piperazinecarbaldehyde C8H16N2O2 详情 详情
(IX) 27737 1-(2-methoxyethyl)piperazine C7H16N2O 详情 详情
(X) 27738 1-(4-chlorophenyl)-3-[[4-(2-methoxyethyl)-1-piperazinyl]methyl]-2-pyrrolidinone C18H26ClN3O2 详情 详情
Extended Information