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【结 构 式】 
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【分子编号】37019 【品名】(1S,2R)-1-allyl-6-fluoro-1,2,3,4-tetrahydro-2-naphthalenamine; (1S,2R)-1-allyl-6-fluoro-1,2,3,4-tetrahydro-2-naphthalenylamine 【CA登记号】 |
【 分 子 式 】C13H16FN 【 分 子 量 】205.2751832 【元素组成】C 76.07% H 7.86% F 9.26% N 6.82% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Condensation of 4-fluorophenylacetyl chloride (I) with ethylene in the presence of AlCl3 provided the beta-tetralone (II). After conversion of (III) into enamine (IV) upon reaction with pyrrolidine (III) in MeOH, alkylation with allyl bromide (V) afforded iminium salt (VI). Acid hydrolysis of (VI) generated the allyl tetralone (VII), which was subjected to reductive amination with ammonium acetate and sodium cyanoborohydride to produce the cis-1-allyl-2-aminotetralin (VIII) as the major isomer. Coupling of (VIII) with carboxylic acid (IX) using 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) gave amide (X), which was finally reduced to the target aminotetralin derivative with LiAlH4.
| 【1】 Lovenberg, T.W.; McNally, J.J.; Youngman, M.A.; et al.; alpha-Substituted N-(sulfonamido)alkyl-beta-aminotetralins: Potent and selective neuropeptide Y Y5 receptor antagonists. J Med Chem 2000, 43, 3, 346. |
| 【2】 Reitz, A.B.; Lovenberg, T.W.; Dax, S.L.; Youngman, M.A.; McNally, J.J. (Ortho-McNeil Pharmaceutical, Inc.); N-Substd. aminotetralins as ligands for the neuropeptide Y Y5 receptor useful in the treatment of obesity and other disorders. WO 9955667 . |
| 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) | 37014 | 2-(4-fluorophenyl)acetyl chloride | 459-04-1 | C8H6ClFO | 详情 | 详情 |
| (II) | 37015 | 6-fluoro-3,4-dihydro-2(1H)-naphthalenone | C10H9FO | 详情 | 详情 | |
| (III) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (IV) | 37016 | 1-(6-fluoro-3,4-dihydro-2-naphthalenyl)pyrrolidine | C14H16FN | 详情 | 详情 | |
| (V) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (VI) | 37017 | 1-[1-allyl-6-fluoro-3,4-dihydro-2(1H)-naphthalenylidene]pyrrolidinium bromide | C17H21BrFN | 详情 | 详情 | |
| (VII) | 37018 | 1-allyl-6-fluoro-3,4-dihydro-2(1H)-naphthalenone | C13H13FO | 详情 | 详情 | |
| (VIII) | 37019 | (1S,2R)-1-allyl-6-fluoro-1,2,3,4-tetrahydro-2-naphthalenamine; (1S,2R)-1-allyl-6-fluoro-1,2,3,4-tetrahydro-2-naphthalenylamine | C13H16FN | 详情 | 详情 | |
| (IX) | 37020 | 4-[[(phenylsulfonyl)amino]methyl]cyclohexanecarboxylic acid | C14H19NO4S | 详情 | 详情 | |
| (X) | 37021 | N-[(1S,2R)-1-allyl-6-fluoro-1,2,3,4-tetrahydro-2-naphthalenyl]-4-[[(phenylsulfonyl)amino]methyl]cyclohexanecarboxamide | C27H33FN2O3S | 详情 | 详情 |