McN-5652Z
Chemical Name: (6S,19bR)-1,2,3,5,6,10b-Hexahydro-6-[4-(methylsulfanyl)phenyl]pyrrolo[2,1-a]isoquinoline perchlorate
CAS No. 90390-80-0, 90390-64-0 (free base)
项目整合开发状态: Preclinical
项目研究机构: Ortho-McNeil (Originator)
合成路线:4-(Methylsulfanyl)mandelic acid and 2-phenylpyrrolidine (I) are heated in refluxing xylene with azeotropic removal of water.The resulting mandelamide (III) is cyclized in polyphosphoric acid at 100 C to a mixture of two diastereomeric lactams.The desired isomer,the minor component (ca- 35%),is separated by preparative HPLC and reduced with borane tetrahydrofuran to the final product.The perchlorate salt crystallizes from 2-propanol on treatment of the free base with the requisite amount of 70% perchloric acid.
📌 参考资料/链接：
参考文献标题:McN-5707 and McN-5652-Z
文献作者:Gardocki,J.F.; Shank,R.P.; Maryanoff,B.E.
参考来源:Drugs Fut 1986,11(1),18
📄 详细内容
合成路线:4-(Methylsulfanyl)mandelic acid and 2-phenylpyrrolidine (I) are heated in refluxing xylene with azeotropic removal of water.The resulting mandelamide (III) is cyclized in polyphosphoric acid at 100 C to a mixture of two diastereomeric lactams.The desired isomer,the minor component (ca- 35%),is separated by preparative HPLC and reduced with borane tetrahydrofuran to the final product.The perchlorate salt crystallizes from 2-propanol on treatment of the free base with the requisite amount of 70% perchloric acid.
合成路线:2-Chlorostyrene oxide is condensed with 2-phenylpyrrolidine in refluxing ethanol,and the resultant amino alcohol (II) is cyclized in polyphosphoric acid at 100 C to a mixture of two diastereomeric amines.The desired diastereomer,the minor component (ca.25%),is separated readily by preparative HPLC.The hydrobromide salt crystallizes from 2-propanol on treatment ot the free base with the requisite amount of 48% HBr.
参考文献标题:Pyrroloisoquinoline antidepressants.Potent,enantioselective inhibition of tetrabenazine-induced ptosis and neuronal uptake of norepinephrine,dopamine,and serotonin
文献作者:Maryanoff,B.E.; McComsey,D.F.; Castanzo,M.J.; Setler,P.E.; Gardocki,J.F.; Shank,R.P.; Schneider,C.R.
参考来源:J Med Chem 1984,27(8),943