CNS-5655(racemate), CNS-5788
Chemical Name: (+)-N1-[2-Chloro-5-(methylsulfanyl)phenyl]-N3-methyl-N3-[3-[(R)-methylsulfinyl]phenyl]guanidine
CAS No. 222734-66-9, 222734-67-0 (acetate), 222734-64-7 (enantiomer), 222734-69-2 (racemate)
项目整合开发状态: Preclinical
项目研究机构: CeNeS (Originator)
合成路线:Oxidation of N-methyl-3-(methylsulfanyl)aniline (I) using hydrogen peroxide in acetone gave the required sulfoxide along with some sulfone,which was removed by chromatography on silica gel.After conversion to the corresponding hydrochloride salt (II),its condensation with 2-chloro-5-(methylthio)phenyl cyanamide (III) in boiling toluene furnished guanidine (IV) (1).The racemic mixture of sulfoxides was finally resolved by chiral HPLC on a Chiralpak AD column to provide the title (R)-enantioner.
合成路线:An asymmetric alternative synthesis has been reported,involving the chiral oxidation of sulfide (I) with (R)-(-)-(8,8-dichloro-10-camphorsulfonyl)oxaziridine (DCCSO) to the desired (R)-sulfoxide (V).Conversion to the hydrochloride salt,followed by condensation with cyanamide (III) afforded the title chiral compound.
📌 参考资料/链接：
参考文献标题:Pharmaceutically active cpd.and methods of use
文献作者:Durant,G.J.; Fischer,J.B.; Perlman,M.; Padmanabhan,S.(Cambridge NeuroScience,Inc.)
参考来源:WO 9918962
📄 详细内容
合成路线:Oxidation of N-methyl-3-(methylsulfanyl)aniline (I) using hydrogen peroxide in acetone gave the required sulfoxide along with some sulfone,which was removed by chromatography on silica gel.After conversion to the corresponding hydrochloride salt (II),its condensation with 2-chloro-5-(methylthio)phenyl cyanamide (III) in boiling toluene furnished guanidine (IV) (1).The racemic mixture of sulfoxides was finally resolved by chiral HPLC on a Chiralpak AD column to provide the title (R)-enantioner.
合成路线:An asymmetric alternative synthesis has been reported,involving the chiral oxidation of sulfide (I) with (R)-(-)-(8,8-dichloro-10-camphorsulfonyl)oxaziridine (DCCSO) to the desired (R)-sulfoxide (V).Conversion to the hydrochloride salt,followed by condensation with cyanamide (III) afforded the title chiral compound.
参考文献标题:Synthesis of potential ischemia-selective NMDA antagonists
文献作者:Fischer,J.B.; Holt,W.H.; Zhou,D.; McBurney,R.N.; Durant,G.J.; Berlove,D.; Lavin,R.C.; Moore,D.; Padmanabhan,S.; Perlman,M:E.
参考来源:219th ACS Natl Meet (March 26 2000,San Francisco) 2000,Abst MEDI 95