合成路线:1) The reaction of 2-(4-piperazinyl)ethanol (I) with diphenylmethyl bromide (II) by means of K2CO3 in DMF gives 2-[4-(diphenylmethyl)-1-piperazinyl] ethanol (III),which is condensed with diketene (IV) at 80 C to yield 2-[4-(diphenylmethyl)-1-piperazinyl] ethyl acetoacetate (V).The condensation of (V) with 3-nitrobenzaldehyde (VI) gives the intermediate benzylidene derivative (VII),which is finally cyclized with methyl 3-aminocrotonate (VIII) in refluxing isopropanol.
合成路线:2) The reaction of 2-(4-piperazinyl)ethanol (I) with diphenylmethyl bromide (II) by means of K2CO3 in DMF gives 2-[4-(diphenylmethyl)-1-piperazinyl] ethanol (III),which is condensed with diketene (IV) at 80 C to yield 2-[4-(diphenylmethyl)-1-piperazinyl] ethyl acetoacetate (V).The reaction of acetoacetate (V) with NH3 in ethanol gives the corresponding aminocrotonate (IX),which is then cyclized with methyl (3-nitrobenzylidene)acetoacetate (VI) [prepared from methyl acetoacetate (X) and 3-nitrobenzaldehyde (VI)] in refluxing isopropanol.
合成路线:3) By cyclization of acetoacetate (V) with aldehyde (VI) and methyl 3-aminocrotonate (VIII) in refluxing isopropanol.
合成路线:4) By cyclization of aldehyde (VI) with aminocrotonate (IX) and methyl acetoacetate (X) in refluxing isopropanol.
参考文献标题:CV-4093
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1988,13(3),207
合成路线:A synthesis of the (R)- and (S)-isomers of manidipine hydrochloride has been described:The cyclization of 3-nitrobenzaldehyde (I) with methyl 3-aminocrotonate (II) and methylacetylacetate (III) gives 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (IV),which is alkylated with ethoxymethyl chloride and NaH yielding the 1-(ethoxymethyl) derivative (V).Selective hydrolysis of (V) with 1-(dimethylamino)-2-propanol - Na - H2O affords the monomethyl ester (VI),which is submitted to optical resolution with cinchonidine and cinchonine giving (R)-1-(ethoxymethyl-5-(methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)- 1,4-dihydropyridine-3-carboxylic acid (VIII) and the corresponding (S)-isomer (IX),respectively.The cleavage of the ethoxymethyl group of (VIII) and (IX) in acidic medium affords the corresponding free (R)-5-(methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyrid ine-3-carboxylic acid (X) and the (S)-isomer (XI).Both compounds are esterified with 2-[4-(diphenylmethyl)piperazin-1-yl]ethanol (XII) by means of PCl5 and NaHCO3,finally yielding the (S)- and (R)-isomers of manidipine hydrochloride,respectively.
参考文献标题:Synthesis and biological activities of optical isomers of 2-(4-diphenylmethyl-1-piperazinyl)ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (manidipine) dihydrochloride
文献作者:Wada,Y.; Kajino,M.; Nagai,Y.; Meguro,K.; Nagaoka,A.
参考来源:Chem Pharm Bull 1989,37(8),2225-8
合成路线:1) The reaction of 2-(4-piperazinyl)ethanol (I) with diphenylmethyl bromide (II) by means of K2CO3 in DMF gives 2-[4-(diphenylmethyl)-1-piperazinyl] ethanol (III),which is condensed with diketene (IV) at 80 C to yield 2-[4-(diphenylmethyl)-1-piperazinyl] ethyl acetoacetate (V).The condensation of (V) with 3-nitrobenzaldehyde (VI) gives the intermediate benzylidene derivative (VII),which is finally cyclized with methyl 3-aminocrotonate (VIII) in refluxing isopropanol.
合成路线:2) The reaction of 2-(4-piperazinyl)ethanol (I) with diphenylmethyl bromide (II) by means of K2CO3 in DMF gives 2-[4-(diphenylmethyl)-1-piperazinyl] ethanol (III),which is condensed with diketene (IV) at 80 C to yield 2-[4-(diphenylmethyl)-1-piperazinyl] ethyl acetoacetate (V).The reaction of acetoacetate (V) with NH3 in ethanol gives the corresponding aminocrotonate (IX),which is then cyclized with methyl (3-nitrobenzylidene)acetoacetate (VI) [prepared from methyl acetoacetate (X) and 3-nitrobenzaldehyde (VI)] in refluxing isopropanol.
合成路线:3) By cyclization of acetoacetate (V) with aldehyde (VI) and methyl 3-aminocrotonate (VIII) in refluxing isopropanol.
合成路线:4) By cyclization of aldehyde (VI) with aminocrotonate (IX) and methyl acetoacetate (X) in refluxing isopropanol.
参考文献标题:New 1,4-dihydropyridine derivatives with potent an
文献作者:Meguro,K.; Aizawa,M.; Sohda,T.; Kawamatsu,Y.; Nagaoka,A.
参考来源:Chem Pharm Bull 1985,33(9),3787
产品链接: CAS No. 120092-68-4›› 产品链接: CAS No.89226-50-6››