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【结 构 式】

【分子编号】54889

【品名】(4S)-4-ethyl-4-hydroxy-7-({7-iodo-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinolin-8-yl}methyl)-1H-pyrano[3,4-c]pyridine-3,8(4H,7H)-dione

【CA登记号】

【 分 子 式 】C28H31IN4O6

【 分 子 量 】646.48197

【元素组成】C 52.02% H 4.83% I 19.63% N 8.67% O 14.85%

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:(XXIX)

Lithiation of 2-methoxypyridine (XVIII), followed by formylation with N-formyl-N,N',N'-trimethylethylenediamine (XIX), produced the pyridine carbaldehyde (XX), which was further iodinated to (XXI) by lithiation and subsequent treatment with iodine. Reductive condensation of aldehyde (XXI) with crotyl alcohol (XXII) in the presence of triethylsilane and trifluoroacetic acid yielded the crotyl ether (XXIII). Cyclization of (XXIII) under Heck reaction conditions led to a mixture of the ethylidene pyranopyridine (XXIV) and the major isomerized analogue (XXV). Sharpless asymmetric dihydroxylation of this reaction mixture afforded the alpha-hydroxy lactol (XXVI), which was further oxidixed to hydroxy lactone (XXVII) employing iodine and CaCO3. Demethylation of ether (XXVII) under acidic conditions generated lactam (XXVIII). Mitsunobu coupling between lactam (XXVIII) and (hydroxymethyl)quinoline (XVII) furnished adduct (XXIX). The title compound was finally obtained by Heck cyclization of (XXIX) in the presence of palladium acetate and triphenylphosphine.

1 Fang, F.G.; et al.; Convergent catalytic asymmetric synthesis of camptothecin analog GI147211C. Tetrahedron 1997, 53, 32, 10953.
2 Fang, F.G.; Xie, S.; Lowery, M.W. (GlaxoSmithKline Inc.); Intermediates in pharmaceutical camptothecin preparation. WO 9529917 .
3 Huie, E.M.; Fang, F.G.; Xie, S.; Comins, D.L. (GlaxoSmithKline Inc.; North Carolina State University); Preparation of a camptothecin deriv. by intramolecular cyclisation. WO 9529919 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XVII) 54877 {7-iodo-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinolin-8-yl}methanol C18H22IN3O3 详情 详情
(XVIII) 54878 2-Methoxypyridine; Methyl 2-pyridyl ether 1628-89-3 C6H7NO 详情 详情
(XIX) 54879 2-(dimethylamino)ethyl(methyl)formamide C6H14N2O 详情 详情
(XX) 54880 2-methoxynicotinaldehyde C7H7NO2 详情 详情
(XXI) 54881 4-iodo-2-methoxynicotinaldehyde C7H6INO2 详情 详情
(XXII) 54882 2-Butene-1-ol; Crotyl Alcohol; trans-Propenylcarbinol 504-61-0 C4H8O 详情 详情
(XXIII) 54883 (E)-2-butenyl (4-iodo-2-methoxy-3-pyridinyl)methyl ether; 3-{[(E)-2-butenyloxy]methyl}-4-iodo-2-methoxypyridine C11H14INO2 详情 详情
(XXIV) 54884 4-[(E)ethylidene]-3,4-dihydro-1H-pyrano[3,4-c]pyridin-8-yl methyl ether; 4-[(E)ethylidene]-8-methoxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine C11H13NO2 详情 详情
(XXV) 54885 4-ethyl-1H-pyrano[3,4-c]pyridin-8-yl methyl ether; 4-ethyl-8-methoxy-1H-pyrano[3,4-c]pyridine C11H13NO2 详情 详情
(XXVI) 54886 (4S)-4-ethyl-8-methoxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine-3,4-diol C11H15NO4 详情 详情
(XXVII) 54887 (4S)-4-ethyl-4-hydroxy-8-methoxy-1,4-dihydro-3H-pyrano[3,4-c]pyridin-3-one C11H13NO4 详情 详情
(XXVIII) 54888 (4S)-4-ethyl-4-hydroxy-1H-pyrano[3,4-c]pyridine-3,8(4H,7H)-dione C10H11NO4 详情 详情
(XXIX) 54889 (4S)-4-ethyl-4-hydroxy-7-({7-iodo-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinolin-8-yl}methyl)-1H-pyrano[3,4-c]pyridine-3,8(4H,7H)-dione C28H31IN4O6 详情 详情
Extended Information