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【结 构 式】

【分子编号】35100

【品名】5-ethyl-5-hydroxy-7-iodo-9-methoxy-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one

【CA登记号】

【 分 子 式 】C12H14INO4

【 分 子 量 】363.15197

【元素组成】C 39.69% H 3.89% I 34.95% N 3.86% O 17.62%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(V)

The known enol ether (I) was dihydroxylated with OsO4 and then oxidatively cleaved to the keto formate (II) by means of Pb(OAc)4. Reformatskii reaction of (II) with (tert-butoxycarbonyl)methylzinc bromide gave hydroxyester (III). Further cyclization of (III) using trifluroacetic acid produced lactone (IV). Halogenation with iodine monochloride afforded iodopyridine (V). Then, cleavage of the methyl ether of (V) employing trimethylsilyl iodide generated the pyridone lactone (VI), which was N-alkylated with 3-(trimethylsilyl)propargyl bromide (VII), yielding (VIII). Radical annulation of (VIII) with isonitrile (IX) in the presence hexamethylditin furnished the pentacyclic system (X). Finally, removal of the N-Boc protecting group of (X) yielded the title compound.

1 Bom, D.; et al.; Novel A,B,E-ring-modified camptothecins displaying high lipophilicity and markedly improved human blood stabilities. J Med Chem 1999, 42, 16, 3018.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
40586 bromo[2-(tert-butoxy)-2-oxoethyl]zinc C6H11BrO2Zn 详情 详情
(I) 35096 4-ethyl-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridin-8-yl methyl ether; 4-ethyl-8-methoxy-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridine C14H21NO2Si 详情 详情
(II) 35097 [2-methoxy-4-propionyl-6-(trimethylsilyl)-3-pyridinyl]methyl formate C14H21NO4Si 详情 详情
(III) 35098 tert-butyl 3-[3-[(formyloxy)methyl]-2-methoxy-6-(trimethylsilyl)-4-pyridinyl]-3-hydroxypentanoate C20H33NO6Si 详情 详情
(IV) 35099 5-ethyl-5-hydroxy-9-methoxy-7-(trimethylsilyl)-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one C15H23NO4Si 详情 详情
(V) 35100 5-ethyl-5-hydroxy-7-iodo-9-methoxy-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one C12H14INO4 详情 详情
(VI) 35101 5-ethyl-5-hydroxy-7-iodo-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione C11H12INO4 详情 详情
(VII) 35105 (3-bromo-1-propynyl)(trimethyl)silane 38002-45-8 C6H11BrSi 详情 详情
(VIII) 35106 5-ethyl-5-hydroxy-7-iodo-8-[3-(trimethylsilyl)-2-propynyl]-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione C17H22INO4Si 详情 详情
(IX) 35107 Carbamic acid, (4-cyanophenyl)-, 1,1-dimethylethyl ester (9CI); tert-butyl 4-cyanophenylcarbamate 143090-18-0 C12H14N2O2 详情 详情
(X) 35108 tert-butyl 5-ethyl-5-hydroxy-3,15-dioxo-12-(trimethylsilyl)-4,5,13,15-tetrahydro-1H,3H-oxepino[3',4':6,7]indolizino[1,2-b]quinolin-10-ylcarbamate C29H35N3O6Si 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

The known enol ether (I) was dihydroxylated with OsO4 and then oxidatively cleaved to the keto formate (II) by means of Pb(OAc)4. Reformatskii reaction of (II) with (tert-butoxycarbonyl)methylzinc bromide gave hydroxyester (III). Further cyclization of (III) using trifluroacetic acid produced lactone (IV). Halogenation with iodine monochloride afforded iodopyridine (V). Then, cleavage of the methyl ether of (V) employing trimethylsilyl iodide generated the pyridone lactone (VI), which was N-alkylated with 3-(tert-butyldimethylsilyl)propargyl bromide (VII), yielding (VIII). Finally, radical annulation of (VIII) with phenyl isonitrile (IX) in the presence hexamethylditin furnished the title pentacyclic compound.

1 Bom, D.; et al.; Novel A,B,E-ring-modified camptothecins displaying high lipophilicity and markedly improved human blood stabilities. J Med Chem 1999, 42, 16, 3018.
2 Burke, T.G.; Curran, D.P.; Bom, D. (University of Kentucky; University of Pittsburgh); Camptothecin analogs and methods of preparation thereof. WO 0061146 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
40586 bromo[2-(tert-butoxy)-2-oxoethyl]zinc C6H11BrO2Zn 详情 详情
(I) 35096 4-ethyl-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridin-8-yl methyl ether; 4-ethyl-8-methoxy-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridine C14H21NO2Si 详情 详情
(II) 35097 [2-methoxy-4-propionyl-6-(trimethylsilyl)-3-pyridinyl]methyl formate C14H21NO4Si 详情 详情
(III) 35098 tert-butyl 3-[3-[(formyloxy)methyl]-2-methoxy-6-(trimethylsilyl)-4-pyridinyl]-3-hydroxypentanoate C20H33NO6Si 详情 详情
(IV) 35099 5-ethyl-5-hydroxy-9-methoxy-7-(trimethylsilyl)-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one C15H23NO4Si 详情 详情
(V) 35100 5-ethyl-5-hydroxy-7-iodo-9-methoxy-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one C12H14INO4 详情 详情
(VI) 35101 5-ethyl-5-hydroxy-7-iodo-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione C11H12INO4 详情 详情
(VII) 35102 (3-bromo-1-propynyl)(tert-butyl)dimethylsilane C9H17BrSi 详情 详情
(VIII) 35103 8-[3-[tert-butyl(dimethyl)silyl]-2-propynyl]-5-ethyl-5-hydroxy-7-iodo-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione C20H28INO4Si 详情 详情
(IX) 35104 Benzonitrile 100-47-0 C7H5N 详情 详情
Extended Information