新产品编号:1819809

合成路线:Catalytic hydrogenation of tetrahydropyridine (I) produced piperidine (II).Alkylation of (II) with N-(3-bromopropyl)phthalimide (III) gave (IV).Subsequent hydrazinolysis of the phthalimido group of (IV) yielded amine (V).In a related procedure,piperidine (II) was alkylated with N-Boc-3-bromopropylamine (VI) to give (VII),which was deprotected with HCl in EtOAc to give the diamino precursor (V).

合成路线:The cyclization between 3,4-difluorobenzaldehyde (VIII),methyl 4-methoxyacetoacetate (IX) and urea (X) in the presence of cuprous oxide and boron trifluoride etherate gave rise to racemic pyrimidinone (XI).Optical resolution of (XI) by means of chiral HPLC furnished the desired (-)-enantiomer (XII),which was then hydrolyzed to carboxylic acid (XIII).Alternatively,kinetic resolution of (XI) by enzymatic hydrolysis using subtilistin furnished the desired (-)-carboxylic acid (XIII),which was then separated from the unreacted (+)-ester.Finally,coupling of carboxylic acid (XIII) with amine (V) using EDC and HOBt yielded the title amide.

参考文献标题:Dihydropyrimidinone C-5 amides as potent and selective alpha1A receptor antagonists
文献作者:Rittle,K.; et al.
参考来源:219th ACS Natl Meet (March 26 2000,San Francisco) 2000,Abst MEDI 90


合成路线:Catalytic hydrogenation of tetrahydropyridine (I) produced piperidine (II).Alkylation of (II) with N-(3-bromopropyl)phthalimide (III) gave (IV).Subsequent hydrazinolysis of the phthalimido group of (IV) yielded amine (V).In a related procedure,piperidine (II) was alkylated with N-Boc-3-bromopropylamine (VI) to give (VII),which was deprotected with HCl in EtOAc to give the diamino precursor (V).

合成路线:The cyclization between 3,4-difluorobenzaldehyde (VIII),methyl 4-methoxyacetoacetate (IX) and urea (X) in the presence of cuprous oxide and boron trifluoride etherate gave rise to racemic pyrimidinone (XI).Optical resolution of (XI) by means of chiral HPLC furnished the desired (-)-enantiomer (XII),which was then hydrolyzed to carboxylic acid (XIII).Alternatively,kinetic resolution of (XI) by enzymatic hydrolysis using subtilistin furnished the desired (-)-carboxylic acid (XIII),which was then separated from the unreacted (+)-ester.Finally,coupling of carboxylic acid (XIII) with amine (V) using EDC and HOBt yielded the title amide.
参考文献标题:In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and selective alpha1A receptor antagonists for the treatment of benign prostatic hyperplasia
文献作者:Barrow,J.C.; Nanterment,P.G.; Selnick,H.G.; Glass,K.L.; Rittle,K.E.; Gilbert,K.F.; Steele,T.G.; Homnick,C.F.; Freidinger,R.M.; Ransom,R.W.; Kling,P.; Reiss,D.R.; Broten,T.P.; Schorn,T.W.; Chang,R.S.; O'Malley,S.S.; Olah,T.V.; et al.
参考来源:J Med Chem 2000,43(14),2703