CRA-0165
Chemical Name: N-Ethyl-N-[4-isopropyl-2-(methylsulfanyl)phenyl]-4-methyl-6-[5-(2-methylphenyl)-1,2,3,6-tetrahydro-1-pyridinyl]pyrimidin-2-amine
项目整合开发状态: Preclinical
项目研究机构: Taisho (Originator)
合成路线:The Grignard reaction of 1-(tert-butoxycarbonyl)piperidin-4-one (I) with 3-fluorophenylmagnesium bromide (II) in THF gives the tertiary alcohol (III),which is dehydrated with TFA or HCl in dioxane yielding the tetrahydropyridine (IV).The condensation of (IV) with 2,4-dichloro-6-methylpyrimidine (V) by means of DIEA in ethanol affords 2-chloro-4-[4-(3-fluorophenyl)-1,2,3,6-tetrahydropyridin-1-yl]-6-methylpyrimidine (VI),which is further condensed with 4-isopropyl-2-(methylsulfanyl)aniline (VII) by means of DIEA in refluxing ethylene glycol to give the secondary amine (VIII).Finally,this compound is alkylated with ethyl iodide and NaH in DMF.
合成路线:The Grignard reaction of 1-(tert-butoxycarbonyl)piperidin-3-one (I) with 2-methylphenylmagnesium bromide (II) in THF gives the tertiary alcohol (III),which is dehydrated with TFA or HCl in dioxane yielding the tetrahydropyridine (IV).The condensation of (IV) with 2,4-dichloro-6-methylpyrimidine (V) by means of DIEA in ethanol affords 2-chloro-6-methyl-4-[3-(2-methylphenyl)-1,2,3,6-tetrahydropyridin-1-yl]pyrimidine (VI),which is further condensed with 4-isopropyl-2-(methylsulfanyl)aniline (VII) by means of DIEA in refluxing ethylene glycol to give the secondary amine (VIII).Finally,this compound is alkylated with ethyl iodide and NaH in DMF.
📌 参考资料/链接：
参考文献标题:4-Tetrahydropyridylpyrimidine derivs.
文献作者:Okubo,T.; Okuyama,S.; Nakazato,A.; Tomisawa,K.; Aibe,I.; Chaki,S.; Kumagai,T.; Tanaka,H.(Taisho Pharmaceutical Co.,Ltd.)
参考来源:EP 0976745; JP 1999228568; WO 9842699
📄 详细内容
合成路线:The Grignard reaction of 1-(tert-butoxycarbonyl)piperidin-4-one (I) with 3-fluorophenylmagnesium bromide (II) in THF gives the tertiary alcohol (III),which is dehydrated with TFA or HCl in dioxane yielding the tetrahydropyridine (IV).The condensation of (IV) with 2,4-dichloro-6-methylpyrimidine (V) by means of DIEA in ethanol affords 2-chloro-4-[4-(3-fluorophenyl)-1,2,3,6-tetrahydropyridin-1-yl]-6-methylpyrimidine (VI),which is further condensed with 4-isopropyl-2-(methylsulfanyl)aniline (VII) by means of DIEA in refluxing ethylene glycol to give the secondary amine (VIII).Finally,this compound is alkylated with ethyl iodide and NaH in DMF.
合成路线:The Grignard reaction of 1-(tert-butoxycarbonyl)piperidin-3-one (I) with 2-methylphenylmagnesium bromide (II) in THF gives the tertiary alcohol (III),which is dehydrated with TFA or HCl in dioxane yielding the tetrahydropyridine (IV).The condensation of (IV) with 2,4-dichloro-6-methylpyrimidine (V) by means of DIEA in ethanol affords 2-chloro-6-methyl-4-[3-(2-methylphenyl)-1,2,3,6-tetrahydropyridin-1-yl]pyrimidine (VI),which is further condensed with 4-isopropyl-2-(methylsulfanyl)aniline (VII) by means of DIEA in refluxing ethylene glycol to give the secondary amine (VIII).Finally,this compound is alkylated with ethyl iodide and NaH in DMF.
参考文献标题:CRF1 receptor antagonists: Aryl-1,2,3,6-tetrahydropyridinopyrimidine derivatives
文献作者:Chaki,S.; Nakazato,A.; Okubo,T.; Kumagai,T.; Tomisawa,K.; Okuyama,S.
参考来源:Symp Med Chem 1998,Abst 1-P-26