【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 |