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【结 构 式】 
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【分子编号】59277 【品名】[3-(3,4-dichlorophenyl)-3-(3-hydroxypropyl)-1-piperidinyl](phenyl)methanone 【CA登记号】 |
【 分 子 式 】C21H23Cl2NO2 【 分 子 量 】392.32456 【元素组成】C 64.29% H 5.91% Cl 18.07% N 3.57% O 8.16% |
合成路线1
该中间体在本合成路线中的序号：(XXVI)In a related synthesis, (3,4-dichlorophenyl)acetonitrile (XI) was alkylated with bromide (XXII) --prepared by protection of 3-bromopropanol (XXI) with dihydropyran-- to afford (XXIII). Subsequent Michael addition of methyl acrylate (XII) to (XXIII) in the presence of Triton B® gave the cyanoacid (XXIV). This was cyclized to the glutarimide (XXV) by refluxing in HOAc in the presence of H2SO4. Reduction of (XXV) using borane-dimethylsulfide complex produced the already reported racemic piperidinoalcohol (XVI). After acylation of the amine group of (XVI) with benzoyl chloride to yield (XXVI), its hydroxyl group was converted into the target mesylate precursor (XXVII) with methanesulfonyl chloride and Et3N.
| 【1】 Giardina, G.A.M.; et al.; A reliable and efficient synthesis of SR 142801. Bioorg Med Chem Lett 1996, 6, 19, 2307. |
| 【2】 Chen, H.G.; et al.; A practical and scalable synthesis of SR 142801, a tachykinin NK3 antagonist. Bioorg Med Chem Lett 1997, 7, 5, 555. |
| 【3】 Grugni, M.; Rigolio, R.; Erhard, K.F. (GlaxoSmithKline Inc.; GlaxoSmithKline SpA); Process for the preparation of 3,3-disubstd. piperidines. WO 9805640 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 26935 | 2-(3,4-dichlorophenyl)acetonitrile | 3218-49-3 | C8H5Cl2N | 详情 | 详情 |
| (XII) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
| (XVI) | 29465 | 3-[3-(3,4-dichlorophenyl)-3-piperidinyl]-1-propanol | C14H19Cl2NO | 详情 | 详情 | |
| (XXI) | 12573 | 3-Bromo-1-propanol; 3-Bromopropanol | 627-18-9 | C3H7BrO | 详情 | 详情 |
| (XXII) | 42252 | 3-bromopropyl tetrahydro-2H-pyran-2-yl ether; 2-(3-bromopropoxy)tetrahydro-2H-pyran | C8H15BrO2 | 详情 | 详情 | |
| (XXIII) | 59274 | 2-(3,4-dichlorophenyl)-5-(tetrahydro-2H-pyran-2-yloxy)pentanenitrile | C16H19Cl2NO2 | 详情 | 详情 | |
| (XXIV) | 59275 | 4-cyano-4-(3,4-dichlorophenyl)-7-(tetrahydro-2H-pyran-2-yloxy)heptanoic acid | C19H23Cl2NO4 | 详情 | 详情 | |
| (XXV) | 59276 | 3-[3-(3,4-dichlorophenyl)-2,6-dioxo-3-piperidinyl]propyl acetate | C16H17Cl2NO4 | 详情 | 详情 | |
| (XXVI) | 59277 | [3-(3,4-dichlorophenyl)-3-(3-hydroxypropyl)-1-piperidinyl](phenyl)methanone | C21H23Cl2NO2 | 详情 | 详情 | |
| (XXVII) | 59278 | 3-[1-benzoyl-3-(3,4-dichlorophenyl)-3-piperidinyl]propyl methanesulfonate | C22H25Cl2NO4S | 详情 | 详情 |