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Acotiamide hydrochloride hydrate, YM-443, Z-338

盐酸阿考替胺 阿考替胺 Chemical Name: N-[4-[N-[2-(Diisopropylamino)ethyl]carbamoyl]thiazol-2-yl]-2-hydroxy-4,5-dimethoxybenzamide hydrochloride trihydrate; N-[2-(Diisopropylamino)ethyl]-2-(2-hydroxy-4,5-dimethoxybenzamido)thiazole-4-carboxamide hydrochloride trihydrate
CAS No. 185104-11-4 (anhydrous), 185106-16-5 (free base, anhydrous), 211999-70-1 (maleate), 403651-06-9 (trihydrate)
项目整合开发状态: Phase II
项目研究机构: Zeria (Originator), Yamanouchi (Licensee)
合成路线:Acylation of 2-aminothiazole-4-carboxylic acid ethyl ester (I) with 2,4,5-trimethoxybenzoyl chloride (II) produced the corresponding amide (III).The 2-methoxy group of (III) was then selectively cleaved by treatment with pyridine hydrochloride,yielding the 2-hydroxybenzamide (IV).Finally,displacement of the ethyl ester group of (IV) by N,N-diisopropyl ethanediamine (V) upon heating at 120 C furnished the target compound,which was isolated as the corresponding hydrochloride salt.
📌 参考资料/链接:
参考文献标题:Aminothiazole derivs.,drug containing the same and intermediate in the production of the cpds.
文献作者:Nagasawa,M.; Murata,M.; Nishioka,H.; Kurimoto,T.; Ueki,S.; Kitagawa,O.(Zeria Pharmaceutical Co.,Ltd.)
参考来源:EP 0870765; US 5981557; WO 9636619

📄 详细内容


合成路线:In a closely related procedure,acid chloride (II),prepared by treatment of 2,4,5-trimethoxybenzoic acid (VI) with SOCl2 in hot toluene,was condensed with aminothiazole (I),yielding amide (III).Displacement of the ethyl ester group of (III) by N,N-diisopropyl ethanediamine (V) furnished diamide (VII).Finally,upon formation of the hydrochloride salt of (VII) in isopropanol,the 2-methoxy group was simultaneously cleaved,directly leading to the title compound.

参考文献标题:Process for producing 2-hydroxybenzamide derivs.
文献作者:Suzuki,T.; Ishii,K.; Nagasawa,M.; Nagano,E.; Nishioka,H.; Nakao,R.(Zeria Pharmaceutical Co.,Ltd.)
参考来源:EP 0994108; WO 9858918


合成路线:Acylation of 2-aminothiazole-4-carboxylic acid ethyl ester (I) with 2,4,5-trimethoxybenzoyl chloride (II) produced the corresponding amide (III).The 2-methoxy group of (III) was then selectively cleaved by treatment with pyridine hydrochloride,yielding the 2-hydroxybenzamide (IV).Finally,displacement of the ethyl ester group of (IV) by N,N-diisopropyl ethanediamine (V) upon heating at 120 C furnished the target compound,which was isolated as the corresponding hydrochloride salt.

合成路线:In a closely related procedure,acid chloride (II),prepared by treatment of 2,4,5-trimethoxybenzoic acid (VI) with SOCl2 in hot toluene,was condensed with aminothiazole (I),yielding amide (III).Displacement of the ethyl ester group of (III) by N,N-diisopropyl ethanediamine (V) furnished diamide (VII).Finally,upon formation of the hydrochloride salt of (VII) in isopropanol,the 2-methoxy group was simultaneously cleaved,directly leading to the title compound.
参考文献标题:Z-338
文献作者:Sorbera,L.A.; Castar,J.; Leeson,P.A.
参考来源:Drugs Fut 2003,28(1),26


产品链接: CAS No. 185104-11-4››

产品链接: CAS No.185106-16-5››