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【结 构 式】 
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【分子编号】36236 【品名】ethyl (4aR,8aR)-6-hydroxy-1-propyldecahydro-3-quinolinecarboxylate 【CA登记号】 |
【 分 子 式 】C15H27NO3 【 分 子 量 】269.38432 【元素组成】C 66.88% H 10.1% N 5.2% O 17.82% |
合成路线1
该中间体在本合成路线中的序号：(VI)The cyclization of 4-benzoyloxycyclohexanone (I) with ethyl 2-bromomethylacrylate (II) and propylamine (III) in refluxing toluene gives ethyl 1-propyl-6-benzoyloxy-1,2,3,4,5,6,7,8-octahydroquinoline-3-carboxylate (IV), which is reduced with sodium cyanoborohydride in methanol yielding the corresponding decahydro derivative (V). Debenzoylation of (V) with NaOH in methanol affords the hydroxyquinoline (VI), which is oxidized with CrO3-pyr giving ethyl 1-propyl-6-oxodecahydroquinoline-3-carboxylate (VII). The reaction of (VII) with dimethylformamide dimethylacetal (VIII) in refluxing toluene yields ethyl 1-propyl-6-oxo-7-(dimethylaminomethylene)decahydroquinoline-3-carboxylate (IX), which is cyclized with hydrazine in ethanol affording ethyl 5-propyl-4,4a,5,6,7,8,8a,9-octahydro-2H-pyrazolo[3,4-g]quinoline-7-carboxylic acid (X). The reduction of (X) with LiAlH4 in THF gives the corresponding hydroxymethyl derivative (XI), which is esterified with methanesulfonyl chloride to the mesyl ester (XII). Finally, this compound is treated with methyl mercaptane and NaH in DMF.
| 【1】 Bach, N.; Kornfeld, E.C. (Eli Lilly and Company); Prolactin inhibiting octahydropyrazolo[3,4-g]quinolines. DD 148517; EP 0013787; ES 482087; FR 2446820; FR 2446821; FR 2446822; GB 2040915; GB 2092579; US 4198415 . |
| 【2】 Nohria, Y.; Castaner, J.; Serradell, M.N.; Blancafort, P.; LY-141,865. Drugs Fut 1983, 8, 10, 858. |
| 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) | 16767 | 4-oxocyclohexyl benzoate | C13H14O3 | 详情 | 详情 | |
| (II) | 11328 | ethyl 2-(bromomethyl)acrylate | 17435-72-2 | C6H9BrO2 | 详情 | 详情 |
| (III) | 23923 | 1-propanamine | 107-10-8 | C3H9N | 详情 | 详情 |
| (IV) | 36234 | ethyl 6-(benzoyloxy)-1-propyl-1,2,3,4,5,6,7,8-octahydro-3-quinolinecarboxylate | C22H29NO4 | 详情 | 详情 | |
| (V) | 36235 | ethyl (4aR,8aR)-6-(benzoyloxy)-1-propyldecahydro-3-quinolinecarboxylate | C22H31NO4 | 详情 | 详情 | |
| (VI) | 36236 | ethyl (4aR,8aR)-6-hydroxy-1-propyldecahydro-3-quinolinecarboxylate | C15H27NO3 | 详情 | 详情 | |
| (VII) | 36237 | ethyl (4aR,8aR)-6-oxo-1-propyldecahydro-3-quinolinecarboxylate | C15H25NO3 | 详情 | 详情 | |
| (VIII) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (IX) | 36238 | ethyl (4aR,8aR)-7-[(Z)-(dimethylamino)methylidene]-6-oxo-1-propyloctahydro-3(1H)-quinolinecarboxylate | C18H30N2O3 | 详情 | 详情 | |
| (X) | 36239 | ethyl (4aR,8aR)-5-propyl-4,4a,5,6,7,8,8a,9-octahydro-2H-pyrazolo[3,4-g]quinoline-7-carboxylate | C16H25N3O2 | 详情 | 详情 | |
| (XI) | 36240 | [(4aR,8aR)-5-propyl-4,4a,5,6,7,8,8a,9-octahydro-2H-pyrazolo[3,4-g]quinolin-7-yl]methanol | C14H23N3O | 详情 | 详情 | |
| (XII) | 36241 | [(4aR,8aR)-5-propyl-4,4a,5,6,7,8,8a,9-octahydro-2H-pyrazolo[3,4-g]quinolin-7-yl]methyl methyl sulfone; (4aR,8aR)-7-[(methylsulfonyl)methyl]-5-propyl-4,4a,5,6,7,8,8a,9-octahydro-2H-pyrazolo[3,4-g]quinoline | C15H25N3O2S | 详情 | 详情 |