【药物名称】MS-377
化学结构式(Chemical Structure):
参考文献No.36530
标题:Pyrrolidinone derivs. and their use as antipsychotic medicaments
作者:Mita, N.; Nagase, H.; Iizuka, H.; Oguchi, T.; Sakai, K.; Horikomi, K.; Miwa, T.; Takahashi, S. (Mitsui Chemicals, Inc.)
来源:EP 0839805; JP 1998182602
合成路线图解说明:

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.

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