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【结 构 式】

【分子编号】37232

【品名】2-[(1S,12R)-13-[(E)ethylidene]-9,15-diazatetracyclo[10.3.1.0(2,10).0(3,8)]hexadeca-2(10),3,5,7-tetraen-15-yl]-1-methoxyethyl methyl ether; (1S,12R)-15-(2,2-dimethoxyethyl)-13-[(E)ethylidene]-9,15-diazatetracyclo[10.3.1.0(2,10).0(3,8)]hexadeca-2(10),3,5,7-tetraene

【CA登记号】

【 分 子 式 】C20H26N2O2

【 分 子 量 】326.43872

【元素组成】C 73.59% H 8.03% N 8.58% O 9.8%

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:(XIII)

The asymetric Michael addition of malonic ester (II) to 2-cyclohexenone (I) catalyzed by (R)-ALB and t-BuOK in THF gives the (R)-enantiomer (III), which is cyclized with phenylhydrazine (IV) in hot acetic acid yielding the tetrahydrocarbazole (V). The protection of (V) with Boc2O, TEA and DMAP in dichloromethane gives protected (VI), which is condensed with acetaldehyde (VII) by means of LDA in THF affording crotonate (VIII). The reduction of the ester group of (VIII) with DIBAL, followed by oxidation with MnO2 gives the corresponding aldehyde (IX), which is reductocondensed with 2-aminoacetaldehyde dimethylacetal (XI) by means of titanium tetraisopropoxide and NaBH4 in toluene/methanol providing adduct (XI). The deprotection of (XI) with TFA and anisole gives the free tetrahydrocarbazole (XII), which is cyclized by means of DDQ in THF yielding the tetracyclic compound (XIII). The reduction of the exocyclic double bond of (XIII) with RhCl(PPh3)3 in benzene/isopropanol affords the (S)-ethyl derivative (XIV), which is treated with Et-SH and BF3/Et2O in dichloromethane to give the thioacetal (XV). Finally, this compound is cyclized with DMTSF, LiAlH4 and Raney-Ni in refluxing ethanol.

1 Shimizu, S.; et al.; Catalytic asymmetric synthesis of tubifolidine. J Org Chem 1998, 63, 21, 7547.
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) 26253 2-cyclohexen-1-one;Cyclohex-2-enone;2-cyclohexenone 930-68-7 C6H8O 详情 详情
(II) 19373 dimethyl malonate;Methyl malonate;Propanedioic acid dimethyl ester 108-59-8 C5H8O4 详情 详情
(III) 37225 dimethyl 2-[(1R)-3-oxocyclohexyl]malonate C11H16O5 详情 详情
(IV) 11818 Phenyl hydrazine; 1-Phenylhydrazine 100-63-0 C6H8N2 详情 详情
(V) 37226 methyl 2-[(2R)-2,3,4,9-tetrahydro-1H-carbazol-2-yl]acetate C15H17NO2 详情 详情
(VI) 37227 tert-butyl (2R)-2-(2-methoxy-2-oxoethyl)-1,2,3,4-tetrahydro-9H-carbazole-9-carboxylate C20H25NO4 详情 详情
(VII) 11974 Acetaldehyde 75-07-0 C2H4O 详情 详情
(VIII) 37228 tert-butyl (2R)-2-[(E)-1-(methoxycarbonyl)-1-propenyl]-1,2,3,4-tetrahydro-9H-carbazole-9-carboxylate C22H27NO4 详情 详情
(IX) 37229 tert-butyl (2R)-2-[(E)-1-formyl-1-propenyl]-1,2,3,4-tetrahydro-9H-carbazole-9-carboxylate C21H25NO3 详情 详情
(X) 37158 ethyl 5-[3-(benzyloxy)-2-formylphenoxy]pentanoate C21H24O5 详情 详情
(XI) 37230 tert-butyl (2R)-2-((E)-1-[[(2,2-dimethoxyethyl)amino]methyl]-1-propenyl)-1,2,3,4-tetrahydro-9H-carbazole-9-carboxylate C25H36N2O4 详情 详情
(XII) 37231 (E)-N-(2,2-dimethoxyethyl)-2-[(2R)-2,3,4,9-tetrahydro-1H-carbazol-2-yl]-2-buten-1-amine; N-(2,2-dimethoxyethyl)-N-[(E)-2-[(2R)-2,3,4,9-tetrahydro-1H-carbazol-2-yl]-2-butenyl]amine C20H28N2O2 详情 详情
(XIII) 37232 2-[(1S,12R)-13-[(E)ethylidene]-9,15-diazatetracyclo[10.3.1.0(2,10).0(3,8)]hexadeca-2(10),3,5,7-tetraen-15-yl]-1-methoxyethyl methyl ether; (1S,12R)-15-(2,2-dimethoxyethyl)-13-[(E)ethylidene]-9,15-diazatetracyclo[10.3.1.0(2,10).0(3,8)]hexadeca-2(10),3,5,7-tetraene C20H26N2O2 详情 详情
(XIV) 37233 2-[(1S,12R,13S)-13-ethyl-9,15-diazatetracyclo[10.3.1.0(2,10).0(3,8)]hexadeca-2(10),3,5,7-tetraen-15-yl]-1-methoxyethyl methyl ether; (1S,12R,13S)-15-(2,2-dimethoxyethyl)-13-ethyl-9,15-diazatetracyclo[10.3.1.0(2,10).0(3,8)]hexadeca-2(10),3,5,7-tetraene C20H28N2O2 详情 详情
(XV) 37234 ethyl 2-[(1S,12R,13S)-13-ethyl-9,15-diazatetracyclo[10.3.1.0(2,10).0(3,8)]hexadeca-2(10),3,5,7-tetraen-15-yl]-1-(ethylsulfanyl)ethyl sulfide; (1S,12R,13S)-15-[2,2-bis(ethylsulfanyl)ethyl]-13-ethyl-9,15-diazatetracyclo[10.3.1.0(2,10).0(3,8)]hexadeca-2(10),3,5,7-tetraene C22H32N2S2 详情 详情
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