5-ethyl-5-hydroxy-7-iodo-9-methoxy-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one -Drug Synthesis Database

【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 合成路线2

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.

参考文献中间体

合成目标

【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.

参考文献中间体

合成目标

【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