【药物名称】CP-4632
化学结构式(Chemical Structure):
参考文献No.40897
标题:Aminopiperidine derivs. as integrin alphavbeta3 antagonists
作者:Ajito, K.; Katano, K.; Kubota, D.; Ishikawa, M.; Murakami, S.; Hachisu, M.; Yamamoto, M. (Meiji Seika Kaisha, Ltd.)
来源:EP 1074543; WO 9952872
合成路线图解说明:

Condensation of 4-hydroxypiperidine (I) with methyl 3,4-difluorobenzoate (II) in DMSO yields derivative (III), which is first mesylated with methanesulfonyl chloride (MsCl) and Et3N in CH2Cl2 and then subjected to reaction with NaN3 in DMF to provide azido derivative (IV). Hydrogenation of (IV) over Pd/C in HOAc/H2O/dioxane affords amino derivative (V), which is then condensed with 2-bromopyrimidine (VI) in DMSO in the presence of DIEA, yielding derivative (VII). Methyl ester group of (VII) is then subjected to saponification by means of aqueous NaOH in THF/MeOH, and the resulting carboxylic acid is coupled to diaminopropionate derivative (VIII) in DMF by means of EDC, HOBt and N-methylmorpholine (NMM) to furnish amide (IX). Hydrolysis of the t-butyl ester group of (IX) by treatment with TFA in CH2Cl2 affords carboxylic acid (X), which is finally hydrogenated over Pd/C in dioxane/H2O to give the target compound.

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