【结 构 式】 |
【分子编号】12672 【品名】(4R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid 【CA登记号】 |
【 分 子 式 】C16H16N2O6 【 分 子 量 】332.31292 【元素组成】C 57.83% H 4.85% N 8.43% O 28.89% |
合成路线1
该中间体在本合成路线中的序号:(X)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 |