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【结 构 式】 
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【药物名称】Dezocine, Wy-16225, Dalgan 【化学名称】(-)-13beta-Amino-5,6,7,8,9,10,11alpha,12-octahydro-5alpha-methyl-5,11-methanobenzocyclodecen-3-ol 【CA登记号】53648-55-8 【 分 子 式 】C16H23NO 【 分 子 量 】245.36781 |
【开发单位】Wyeth Pharmaceuticals (Originator), AstraZeneca (Not Determined) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Opioid Analgesics, Opioid Agonists-Antagonists |
合成路线1
Compound is prepared through the following sequence: The condensation of 1-methyl-7-methoxy-2-tetralone (I) with 1,5-dibromopentane (A) by means of NaH or potassium tertbutylate affords 1-(5-bromopentyl)-1-methyl-7-methoxy-2-tetralone (II); this product is cyclized with NaH to give 5-methyl-3-methoxy-5,6,7,8,9,10,11,12-octahydro-5,11-methanobenzocyclodecen-13-one (III). The ketone (III), by reaction with hydroxylamine hydrochloride in pyridine, is converted into its oxime (IV), which is reduced with H2 over Raney-Ni to a mixture of isomeric amines that were separated by crystallization of the HCl salts giving 5alpha-methyl-3-methoxy-5,6,7,8,9,11alpha,12-octahydro-5,11-methanobenzocyclodecen-13beta-amine (V), which is finally submitted to cleavage with concentrated HBr.
| 【1】 Freed, M.E.; Potoski, J.R.; Benzobicycloalkanes compounds. DE 2159324; FR 2116509; GB 1363658; GB 1363659 . |
| 【2】 Freed, M.E.; et al.; Bridged aminotetralins as novel potent analgesic substances. J Med Chem 1973, 16, 6, 595. |
| 【3】 Hopkins, S.J.; Castaner, J.; Dezocine. Drugs Fut 1976, 1, 5, 229. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 30560 | 1,5-dibromopentane | 111-24-0 | C5H10Br2 | 详情 | 详情 |
| (Va) | 33980 | (1R,9S,15R)-4-methoxy-1-methyltricyclo[7.5.1.0(2,7)]pentadeca-2,4,6-trien-15-ylamine; (1R,9S,15R)-4-methoxy-1-methyltricyclo[7.5.1.0(2,7)]pentadeca-2,4,6-trien-15-amine | C17H25NO | 详情 | 详情 | |
| (Vb) | 33981 | (1R,9S,15S)-4-methoxy-1-methyltricyclo[7.5.1.0(2,7)]pentadeca-2,4,6-trien-15-ylamine; (1R,9S,15S)-4-methoxy-1-methyltricyclo[7.5.1.0(2,7)]pentadeca-2,4,6-trien-15-amine | C17H25NO | 详情 | 详情 | |
| (I) | 33976 | 7-methoxy-1-methyl-3,4-dihydro-2(1H)-naphthalenone | C12H14O2 | 详情 | 详情 | |
| (II) | 33977 | 1-(5-bromopentyl)-7-methoxy-1-methyl-3,4-dihydro-2(1H)-naphthalenone | C17H23BrO2 | 详情 | 详情 | |
| (III) | 33978 | 4-methoxy-1-methyltricyclo[7.5.1.0(2,7)]pentadeca-2,4,6-trien-15-one | C17H22O2 | 详情 | 详情 | |
| (IV) | 33979 | 4-methoxy-1-methyltricyclo[7.5.1.0(2,7)]pentadeca-2,4,6-trien-15-one oxime | C17H23NO2 | 详情 | 详情 |