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【结 构 式】

【分子编号】12668

【品名】dimethyl 1-(ethoxymethyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate

【CA登记号】

【 分 子 式 】C20H24N2O7

【 分 子 量 】404.41984

【元素组成】C 59.4% H 5.98% N 6.93% O 27.69%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(V)

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.

1 Wada, Y.; Kajino, M.; Nagai, Y.; Meguro, K.; Nagaoka, A.; 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. Chem Pharm Bull 1989, 37, 8, 2225-8.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 12646 3-Nitrobenzaldehyde 99-61-6 C7H5NO3 详情 详情
(II) 11372 Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate C5H9NO2 详情 详情
(III) 11791 methyl 3-oxobutanoate; Methyl acetoacetate 105-45-3 C5H8O3 详情 详情
(IV) 12667 dimethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate; 2,6-Dimethyl-4-(3-nitro-ph)-1,4-2h-pyridine-3,5-dicarboxylic acid dimethyl ester 21881-77-6 C17H18N2O6 详情 详情
(V) 12668 dimethyl 1-(ethoxymethyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate C20H24N2O7 详情 详情
(VI) 12669 1-(Ethoxymethyl)-5-(methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid C19H22N2O7 详情 详情
(VIII) 12670 (4R)-1-(Ethoxymethyl)-5-(methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid C19H22N2O7 详情 详情
(IX) 12671 (4S)-1-(Ethoxymethyl)-5-(methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid C19H22N2O7 详情 详情
(X) 12672 (4R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid C16H16N2O6 详情 详情
(XI) 12673 (4S)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid C16H16N2O6 详情 详情
(XII) 12674 2-(4-Benzhydryl-1-piperazinyl)-1-ethanol C19H24N2O 详情 详情
Extended Information