NU-1085
1H-苯并咪唑-7-羧酰胺,2-(4-羟基苯基)-Chemical Name: 2-(4-Hydroxyphenyl)-1H-benzimidazole-4-carboxamide
CAS No. 188106-83-4
项目整合开发状态: Preclinical
项目研究机构: University of Newcastle upon Tyne (Originator), Agouron (Codevelopment)
合成路线:Regioselective ring opening of 3-nitrophthalic anhydride (I) with ammonia yielded amide (II),which was subjected to a Hofmann degradation with Br2 and KOH to afford 3-nitroanthranilic acid (III).Esterification of (III) to ster (IV) using MeOH/HCl,followed by reduction of the nitro group by catalytic hydrogenation,gave methyl 2,3-diaminobenzoate (V).Alternatively,diamino ester (V) was prepared by reduction of nitro acid (III),followed by catalytic esterification.Methyl 2,3-diaminobenzoate (V) was then selectively acylated at the 3-amino group with 4-methoxybenzoyl chloride (VI) producing amide (VII),which was cyclized to the benzimidazole (VIII) upon refluxing in HOAc.The corresponding amide (IX) was obtained by reaction of ester (VIII) with liquid ammonia at 100 C in a pressure vessel.Finally,the methyl ether group of (IX) was cleaved to the title phenol by treatment with boron tribromide.
📌 参考资料/链接：
参考文献标题:Benzimidazole cpds.
文献作者:Griffin,R.J.; Calvert,A.H.; Newell,D.R.; Curtain,J.N.; Golding,B.T.(University of Newcastle upon Tyne)
参考来源:US 6100283
📄 详细内容
合成路线:Regioselective ring opening of 3-nitrophthalic anhydride (I) with ammonia yielded amide (II),which was subjected to a Hofmann degradation with Br2 and KOH to afford 3-nitroanthranilic acid (III).Esterification of (III) to ster (IV) using MeOH/HCl,followed by reduction of the nitro group by catalytic hydrogenation,gave methyl 2,3-diaminobenzoate (V).Alternatively,diamino ester (V) was prepared by reduction of nitro acid (III),followed by catalytic esterification.Methyl 2,3-diaminobenzoate (V) was then selectively acylated at the 3-amino group with 4-methoxybenzoyl chloride (VI) producing amide (VII),which was cyclized to the benzimidazole (VIII) upon refluxing in HOAc.The corresponding amide (IX) was obtained by reaction of ester (VIII) with liquid ammonia at 100 C in a pressure vessel.Finally,the methyl ether group of (IX) was cleaved to the title phenol by treatment with boron tribromide.
参考文献标题:Pharmacological actions of a novel,high-affinity,and selective human dopamine D3 receptor antagonist,SB-277011-A
文献作者:Reavill,C.; Taylor,S.G.; Wood,M.D.; Ashmeade,T.; Austin,N.E.; Avenell,K.Y.; Boyfield,I.; Branch,C.L.; Cilia,J.; Coldwell,M.C.; Hadley,M.S.; Hunter,A.J.; Jeffrey,P.; Jewitt,F.; Johnson,C.N.; Jones,D.N.; Medhurst,A.D.; et al.
参考来源:J Pharmacol Exp Ther 2000,294(3),1154
产品链接: CAS No. 188106-83-4››