【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% |
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 |