新产品编号:1063613

合成路线:Alkylation of methyl 4-(acetylamino)-2-hydroxybenzoate (I) with propargyl bromide (II) in the presence of K2CO3 in refluxing acetonitrile gave propargyl ether (III),and subsequent chlorination with N-chlorosuccinimide in DMF yielded (IV).Then,a Claisen-type rearrangement of (IV) in boiling diphenyl ether furnished the benzopyran (V),which was hydrogenated over Pt/C to give dihydrobenzopyran (VI).Subsequent treatment of (VI) with 4 N KOH produced the hydrolysis of both ester and amide functions,affording acid (VII).Treatment of dicyclopropyl ketone (VIII) with HCl gas provided 1,7-dichloro-4-heptanone (IX).Cyclization of (IX) with cyanoacetic acid in a two-phase system of aqueous ammonia and n-hexane gave bicyclic intermediate (X),which upon decarboxylation yielded nitrile (XI).Subsequent hydrogenation in the presence of Raney-Ni and NaOH furnished 5-(2-aminoethyl)-1-azabicyclo[3.3.0]octane (XII) (3).The title compound was then obtained by coupling of acid (VII) with amine (XII) using carbonyldiimidazole (CDI),followed by conversion to the hemifumarate salt.

参考文献标题:Synthesis and structure-activity relationship of 3-substituted benzamide,benzo[b]furan-7-carboxamide,2,3-dihydrobenzo[b]furan-7-carboxamide,and indole-5-carboxamide derivatives as selective serotonin 5-HT4 receptor agonists
文献作者:Kakigami,T.; Usui,T.; Tsukamoto,K.; Kataoka,T.
参考来源:Chem Pharm Bull 1998,46(1),42


合成路线:Alkylation of methyl 4-(acetylamino)-2-hydroxybenzoate (I) with propargyl bromide (II) in the presence of K2CO3 in refluxing acetonitrile gave propargyl ether (III),and subsequent chlorination with N-chlorosuccinimide in DMF yielded (IV).Then,a Claisen-type rearrangement of (IV) in boiling diphenyl ether furnished the benzopyran (V),which was hydrogenated over Pt/C to give dihydrobenzopyran (VI).Subsequent treatment of (VI) with 4 N KOH produced the hydrolysis of both ester and amide functions,affording acid (VII).Treatment of dicyclopropyl ketone (VIII) with HCl gas provided 1,7-dichloro-4-heptanone (IX).Cyclization of (IX) with cyanoacetic acid in a two-phase system of aqueous ammonia and n-hexane gave bicyclic intermediate (X),which upon decarboxylation yielded nitrile (XI).Subsequent hydrogenation in the presence of Raney-Ni and NaOH furnished 5-(2-aminoethyl)-1-azabicyclo[3.3.0]octane (XII) (3).The title compound was then obtained by coupling of acid (VII) with amine (XII) using carbonyldiimidazole (CDI),followed by conversion to the hemifumarate salt.
参考文献标题:A 3D-quantitative structure-activity relationship study of benzamide type serotonin 5-HT4 receptor agonists based on a comparative molecular field analysis model,and the design and synthesis of potent agonists
文献作者:Kakigami,T.; et al.
参考来源:Chem Pharm Bull 1998,46(12),1881