【药物名称】CRA-0165
化学结构式(Chemical Structure):
参考文献No.37502
标题:4-Tetrahydropyridylpyrimidine derivs.
作者:Okubo, T.; Okuyama, S.; Nakazato, A.; Tomisawa, K.; Aibe, I.; Chaki, S.; Kumagai, T.; Tanaka, H. (Taisho Pharmaceutical Co., Ltd.)
来源:EP 0976745; JP 1999228568; WO 9842699
合成路线图解说明:

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.

合成路线图解说明:

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No.476237
标题:CRF1 receptor antagonists: Aryl-1,2,3,6-tetrahydropyridinopyrimidine derivatives
作者:Chaki, S.; Nakazato, A.; Okubo, T.; Kumagai, T.; Tomisawa, K.; Okuyama, S.
来源:Symp Med Chem 1998,Abst 1-P-26
合成路线图解说明:

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.

合成路线图解说明:

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.

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