CEP-7055, -Drug Synthesis Database

【结构式】

【药物名称】CEP-7055

【化学名称】N,N-Dimethylglycine 3-[9-(isopropoxymethyl)-5-oxo-5,6,7,13-tetrahydro-12H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-12-yl]propyl ester

【CA登记号】402857-58-3

【分子式】C₃₂H₃₅N₃O₄

【分子量】525.65345

【开发单位】Ricerca (Supplier), Cephalon (Originator), Sanofi-synthélabo (Licensee)

【药理作用】Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, Oncolytic Drugs, Solid Tumors Therapy, Angiogenesis Inhibitors, Inhibitors of Signal Transduction Pathways, VEGFR Inhibitors

合成路线1 合成路线2

合成路线1

Michael addition of ethyl acrylate (II) to the indenopyrrolocarbazole (I) provided (III). Lactam N-protection of (III) with dimethoxybenzhydrol yielded N-protected ethyl ester (IV), which was reduced with LiBH4 to give alcohol (V). Subsequent bromination of (V) with N-bromosuccinimide yielded (VI), which was first submitted to palladium-catalyzed carbonylation in methoxyethanol and then N-deprotected with trifluoroacetic acid and thioanisole to furnish (VII). Finally, reduction of ester (VII) with DIBAL furnished the diol intermediate (VIII).

参考文献中间体

【1】 Hudkins, R.L.; Gingrich, D.E. (Cephalon, Inc.); Selected fused pyrrolocarbazoles. WO 0217914 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	59386	6,7,12,13-tetrahydro-5H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one		C₂₁H₁₄N₂O	详情	详情
(II)	10164	ethyl acrylate	140-88-5	C₅H₈O₂	详情	详情
(III)	59387	ethyl 3-(5-oxo-5,6,7,13-tetrahydro-12H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-12-yl)propanoate		C₂₆H₂₂N₂O₃	详情	详情
(IV)	59388	ethyl 3-{6-[bis(4-methoxyphenyl)methyl]-5-oxo-5,6,7,13-tetrahydro-12H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-12-yl}propanoate		C₄₁H₃₆N₂O₅	详情	详情
(V)	59389	6-[bis(4-methoxyphenyl)methyl]-12-(3-hydroxypropyl)-6,7,12,13-tetrahydro-5H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one		C₃₉H₃₄N₂O₄	详情	详情
(VI)	59390	6-[bis(4-methoxyphenyl)methyl]-9-bromo-12-(3-hydroxypropyl)-6,7,12,13-tetrahydro-5H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one		C₃₉H₃₃BrN₂O₄	详情	详情
(VII)	59391	2-methoxyethyl 12-(3-hydroxypropyl)-5-oxo-6,7,12,13-tetrahydro-5H-indeno[2,1-a]pyrrolo[3,4-c]carbazole-9-carboxylate		C₂₈H₂₆N₂O₅	详情	详情
(VIII)	59392	9-(hydroxymethyl)-12-(3-hydroxypropyl)-6,7,12,13-tetrahydro-5H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one		C₂₅H₂₂N₂O₃	详情	详情

合成路线2

An alternative route was based on the formylation of (III) with dichloromethyl methyl ether (IX) in the presence of tin chloride. The resultant aldehyde ester (X) was then reduced to the already reported diol (VIII) by means of LiBH4. The crude trifluoroacetate ester obtained by treatment of diol (VIII) with trifluoroacetic anhydride was then refluxed with isopropanol to furnish the isopropyl ether (XI). The remaining hydroxyl group was finally esterified by treatment with N,N-dimethylglycine (XII) in the presence of EDC and DMAP.

参考文献中间体

【1】 Hudkins, R.L.; Gingrich, D.E. (Cephalon, Inc.); Selected fused pyrrolocarbazoles. WO 0217914 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	59387	ethyl 3-(5-oxo-5,6,7,13-tetrahydro-12H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-12-yl)propanoate		C₂₆H₂₂N₂O₃	详情	详情
(VIII)	59392	9-(hydroxymethyl)-12-(3-hydroxypropyl)-6,7,12,13-tetrahydro-5H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one		C₂₅H₂₂N₂O₃	详情	详情
(IX)	40668	dichloro(methoxy)methane; dichloromethyl methyl ether	4885-02-3	C₂H₄Cl₂O	详情	详情
(X)	59393	ethyl 3-(9-formyl-5-oxo-5,6,7,13-tetrahydro-12H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-12-yl)propanoate		C₂₇H₂₂N₂O₄	详情	详情
(XI)	59394	12-(3-hydroxypropyl)-9-(isopropoxymethyl)-6,7,12,13-tetrahydro-5H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one		C₂₈H₂₈N₂O₃	详情	详情
(XII)	16765	2-(dimethylamino)acetic acid; N,N-Dimethylglycine	1118-68-9	C₄H₉NO₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)