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【结 构 式】

【分子编号】30768

【品名】dimethyl 2,3-dihydro-1H-pyrrolizine-1,7-dicarboxylate

【CA登记号】

【 分 子 式 】C11H13NO4

【 分 子 量 】223.22856

【元素组成】C 59.19% H 5.87% N 6.27% O 28.67%

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:(XVIII)

The condensation of dimethylacetone-1,3-dicarboxylate (X) with ethanolamine (XI) yields methyl 3-(methoxycarbonylmethyl)-3-(2-hydroxyethylamino)acrylate (XII), which is cyclized with bromoacetaldehyde diethylacetal (XIII) affording methyl 1-(2-hydroxyethyl)-3-methoxycarbonylpyrrol-2-acetate (XIV). Acylation of (XIV) with methanesulfonyl chloride (XV) and triethylamine in CH2Cl2 yields the corresponding mesylate (XVI), which by treatment with methyl iodide in refluxing acetonitrile is converted into methyl 1-(2-iodoethyl)-3-methoxycarbonylpyrrole-2-acetate (XVII). The cyclization of (XVII) with NaH in DMF yields dimethyl 1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,7-dicarboxylate (XVIII), which is hydrolyzed with KOH in refluxing methanol - water to the corresponding diacid (XIX). Partial esterification of (XIX) with isopropanol and HCl gives isopropyl 1,2-dihydro-3H-7-carboxypyrrolo[1,2-a]pyrrole-1-carboxylate (XX), which is decarboxylated by heating at 270 C affording isopropyl 1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate (XXI). Benzoylation of (XXI) with N,N-dimethylbenzamide (XXII) and POCl3 in refluxing CH2Cl2 yields isopropyl 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate (XXIII), which is finally hydrolyzed with K2CO3 or NaOH in methanol - water.

1 Blancafort, P.; Serradell, M.N.; Hillier, K.; Castaner, J.; BPPC. Drugs Fut 1981, 6, 11, 669.
2 Muchowski, J.M.; Kluge, A.F. (Roche Bioscience); 1,2-Dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids derivatives and process for the production thereof. DE 2731678; ES 460706; ES 470214; FR 2358406; FR 2375234; GB 1554075 .
3 Arrigoni-Martelli, E.; Castaner, J.; Blancafort, P.; Serradell, M.N.; RS-37,619. Drugs Fut 1983, 8, 10, 871.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(X) 22692 dimethyl 3-oxopentanedioate 1830-54-2 C7H10O5 详情 详情
(XI) 10259 Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol;2-Aminoethyl alcohol 141-43-5 C2H7NO 详情 详情
(XII) 30764 dimethyl (E)-3-[(2-hydroxyethyl)amino]-2-pentenedioate C9H15NO5 详情 详情
(XIII) 12113 2-Bromo-1-ethoxyethyl ethyl ether; 2-Bromo-1,1-diethoxyethane; Bromoacetaldehyde diethylacetal 2032-35-1 C6H13BrO2 详情 详情
(XIV) 30765 methyl 1-(2-hydroxyethyl)-2-(2-methoxy-2-oxoethyl)-1H-pyrrole-3-carboxylate C11H15NO5 详情 详情
(XVI) 30766 methyl 2-(2-methoxy-2-oxoethyl)-1-(2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]ethyl)-1H-pyrrole-3-carboxylate C14H21NO5S 详情 详情
(XVII) 30767 methyl 1-(2-iodoethyl)-2-(2-methoxy-2-oxoethyl)-1H-pyrrole-3-carboxylate C11H14INO4 详情 详情
(XVIII) 30768 dimethyl 2,3-dihydro-1H-pyrrolizine-1,7-dicarboxylate C11H13NO4 详情 详情
(XIX) 30769 2,3-dihydro-1H-pyrrolizine-1,7-dicarboxylic acid C9H9NO4 详情 详情
(XX) 30770 1-(isopropoxycarbonyl)-2,3-dihydro-1H-pyrrolizine-7-carboxylic acid C12H15NO4 详情 详情
(XXI) 30771 isopropyl 2,3-dihydro-1H-pyrrolizine-1-carboxylate C11H15NO2 详情 详情
(XXII) 30757 N,N-dimethylbenzamide 611-74-5 C9H11NO 详情 详情
(XXIII) 30772 isopropyl 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylate C18H19NO3 详情 详情
Extended Information