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【结 构 式】

【分子编号】35054

【品名】ethyl 3-(1,3-benzodioxol-5-yl)-4-nitro-2-(4-propoxybenzoyl)butanoate

【CA登记号】

【 分 子 式 】C23H25NO8

【 分 子 量 】443.45344

【元素组成】C 62.3% H 5.68% N 3.16% O 28.86%

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)

Condensation of piperonal (I) with nitromethane in the presence of ammonium acetate in AcOH provided nitrostyrene (II). Ketoester (IV) was prepared by carbethoxylation of 4'-propoxyacetophenone (III) with diethyl carbonate. Subsequent conjugate addition of ketoester (IV) to nitrostyrene (II) using DBU provided adduct (V). Hydrogenation of the nitro group of (V) over Raney Nickel, with concomitant ring closure formed the cyclic imine (VI), and further reduction of (VI) with NaBH3CN yielded the corresponding pyrrolidine as a diastereomeric mixture. Chromatographic separation removed the cis,cis isomer, affording a mixture of trans,trans and cis,trans pyrrolidines (VIIa, VIIb). 2,6-Diethylbromoacetanilide (IX) was prepared by acylation of 2,6-diethylaniline (VIII) with bromoacetyl bromide. N-Alkylation of the mixture of pyrrolidines (VIIa, VIIb) with bromoacetanilide (IX) furnished (Xa, Xb).

1 Sorensen, B.K.; Tasker, A.S.; von Geldern, T.W.; et al.; Pyrrolide-3-carboxylic acids as endothelin antagonists. 4. Side chain conformational restriction leads to ETB selectivity. J Med Chem 1999, 42, 18, 3668.
2 Tasker, A.S.; Boyd, S.A.; Sorensen, B.K.; Winn, M.; Jae, H.-S.; Von Geldern, T.W.; Henry, K.J. (Abbott Laboratories Inc.); 4-(Benzo-1,3-dioxolyl)-pyrrolidine-3-carboxylic acid derivs. as endothelin antagonists. EP 0888340; JP 2000504727; WO 9730046 .
3 Tasker, A.S.; Henry, K.J.; Boyd, S.A.; Von Geldern, T.W.; Sorensen, B.K.; Jae, H.-S.; Winn, M. (Abbott Laboratories Inc.); Pyrrolidine carboxylic acid derivs. as endothelin antagonists. EP 0991620; WO 9857933 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
14005 2-Bromoacetyl bromide; Bromoacetyl bromide 598-21-0 C2H2Br2O 详情 详情
17470 diethyl carbonate; diethylcarbonate 105-58-8 C5H10O3 详情 详情
39563 nitromethane 75-52-5 CH3NO2 详情 详情
(VIIa) 35056 ethyl (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-2-(4-propoxyphenyl)-3-pyrrolidinecarboxylate C23H27NO5 详情 详情
(VIIb) 35057 ethyl (2S,3R,4S)-4-(1,3-benzodioxol-5-yl)-2-(4-propoxyphenyl)-3-pyrrolidinecarboxylate C23H27NO5 详情 详情
(Xa) 35060 ethyl (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethylanilino)-2-oxoethyl]-2-(4-propoxyphenyl)-3-pyrrolidinecarboxylate C35H42N2O6 详情 详情
(Xb),(XI) 35061 ethyl (2S,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethylanilino)-2-oxoethyl]-2-(4-propoxyphenyl)-3-pyrrolidinecarboxylate C35H42N2O6 详情 详情
(I) 10127 1,3-Benzodioxole-5-carbaldehyde; Heliotropine 120-57-0 C8H6O3 详情 详情
(II) 20675 5-[(E)-2-nitroethenyl]-1,3-benzodioxole 1485-00-3 C9H7NO4 详情 详情
(III) 35052 1-(4-propoxyphenyl)-1-ethanone C11H14O2 详情 详情
(IV) 35053 ethyl 3-oxo-3-(4-propoxyphenyl)propanoate C14H18O4 详情 详情
(V) 35054 ethyl 3-(1,3-benzodioxol-5-yl)-4-nitro-2-(4-propoxybenzoyl)butanoate C23H25NO8 详情 详情
(VI) 35055 ethyl 3-(1,3-benzodioxol-5-yl)-5-(4-propoxyphenyl)-3,4-dihydro-2H-pyrrole-4-carboxylate C23H25NO5 详情 详情
(VIII) 35058 2,6-diethylphenylamine; 2,6-diethylaniline 579-66-8 C10H15N 详情 详情
(IX) 35059 2-bromo-N-(2,6-diethylphenyl)acetamide C12H16BrNO 详情 详情
Extended Information