Batanopride hydrochloride, BMY-25801-01, BMY-25801 free base
4-氨基-5-氯-N-(2-二乙基氨基乙基)-2-(3-氧代丁烷-2-基氧基)苯甲酰胺盐酸盐 巴他必利 Chemical Name: (?-4-Amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(1-methyl-2-oxopropoxy)benzamide hydrochloride
CAS No. 102670-59-7, 102670-46-2 (free base)
项目整合开发状态: Phase III
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:The demethylation of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide (I) with EtS-Na in hot DMF gives the hydroxy compound (II),which is acylated with 3-chloro-2-butanone (III) by means of K2CO3 and NaI in DMF to yield 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(1-methyl-2-oxopropoxy)benzamide (IV).Finally,this compound is treated with HCl to furnish the target hydrochloride.Alternatively,the alkylation of the hydroxy compound (II) can also be performed by reaction of (II) with tetrabutylammonium bisulfate and NaOH to give the tetrabutylammonium phenolate (V),which is alkylated with the chlorobutanone (III) to give (IV).
📌 参考资料/链接：
参考文献标题:Substituted benzamides.1.Potential nondopaminergic antagonists of chemotherapy-induced nausea and emesis
文献作者:Monkovic,I.; Willner,D.; Adam,M.A.; Brown,M.; Crenshaw,R.R.; Fuller,C.E.; Juby,P.F.; Luke,G.M.; Matiskella,J.A.; Montzka,T.A.
参考来源:J Med Chem 1988,31(8),1548-58
📄 详细内容
合成路线:The demethylation of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide (I) with EtS-Na in hot DMF gives the hydroxy compound (II),which is acylated with 3-chloro-2-butanone (III) by means of K2CO3 and NaI in DMF to yield 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(1-methyl-2-oxopropoxy)benzamide (IV).Finally,this compound is treated with HCl to furnish the target hydrochloride.Alternatively,the alkylation of the hydroxy compound (II) can also be performed by reaction of (II) with tetrabutylammonium bisulfate and NaOH to give the tetrabutylammonium phenolate (V),which is alkylated with the chlorobutanone (III) to give (IV).
参考文献标题:NEW BENZAMIDE ANTI-EMETICS
文献作者:Monkovic,I.
参考来源:Drugs Fut 1989,14(1),41
合成路线:A new synthesis for [14C]-labeled batanopride has been described:The starting material is 4-amino-2-hydroxybenzoic acid labeled with [14C] at the carboxy group (I).The methylation of (I) in the usual way gives 4-amino-2-methoxybenzoic acid methyl ester (II),which is treated with acetic anhydride to yield the corresponding acetamido derivative (III).Chlorination of (III) with Cl2 in acetic acid affords 4-acetamido-5-chloro-2-methoxybenzoic acid methyl ester (IV),which is hydrolyzed with aqueous NaOH to 4-amino-5-chloro-2-methoxybenzoic acid (V).The condensation of (V) with 2-(diethylamino)ethylamine (VI) by means of triethylamine and isobutyl chloroformate in THF gives the corresponding amide (VII),which is demethylated with sodium ethanethiolate in DMF to yield the phenolate (VIII).The condensation of (VIII) with 3-chloro-2-butanone (IX) in DMF affords batanopride free base (X),which is finally treated with HCl in acetone - water.
参考文献标题:Synthesis of 4-amino-5-chloro-N[2-(diethylamino)ethyl]-2-[(butan-2-on-3-yl)oxy]-[carbonyl-C-14]benzamide hydrochloride (C-14-batanopride)
文献作者:Standridge,R.T.; Swigor,J.E.
参考来源:J Label Compd Radiopharm 1991,29(9),983
产品链接: CAS No. 102670-59-7›› 产品链接: CAS No.102670-46-2››