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【结 构 式】 
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【药物名称】O-2185 【化学名称】4-Pentenoic acid (1R,2R,3R,5S)-3-(3,4-dichlorophenyl)-8-oxabicyclo[3.2.1]oct-2-ylmethyl ester 【CA登记号】 【 分 子 式 】C19H22Cl2O3 【 分 子 量 】369.29139 |
【开发单位】Organix (Originator) 【药理作用】Treatment of Cocaine Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, Dopamine Transporter (DAT) Inhibitors |
合成路线1
Treatment of methyl 3-hydroxy-8-oxabicyclo[3.2.1]oct-2-ene-2-carboxylate (I) with N-phenyl trifluoromethanesulfonimide leads to the vinyl triflate (II). Suzuki coupling of triflate (II) with 3,4-dichlorophenylboronic acid (III) furnishes the oxabicyclooctene adduct (IV), which is further reduced to the oxabicyclooctane (V) with SmI2. Ester reduction in (V) with LiAlH4 provides alcohol (VI). This is finally esterified with 4-pentenoyl chloride (VII) to furnish the title compound.
| 【1】 Meltzer, P.C.; Liu, S.; Blanchette, H.; Blundell, P.; Madras, B.; Design and synthesis of an irreversible dopamine-sparing cocaine antagonist. Bioorg Med Chem 2002, 10, 11, 3583. |
| 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) | 61643 | methyl (1R,5S)-3-hydroxy-8-oxabicyclo[3.2.1]oct-2-ene-2-carboxylate | C9H12O4 | 详情 | 详情 | |
| (II) | 61644 | methyl (1R,5S)-3-{[(trifluoromethyl)sulfonyl]oxy}-8-oxabicyclo[3.2.1]oct-2-ene-2-carboxylate | C10H11F3O6S | 详情 | 详情 | |
| (III) | 34040 | 3,4-Dichlorophenylboronic acid | 151169-75-4 | C6H5BCl2O2 | 详情 | 详情 |
| (IV) | 61645 | methyl (1R,5S)-3-(3,4-dichlorophenyl)-8-oxabicyclo[3.2.1]oct-2-ene-2-carboxylate | C15H14Cl2O3 | 详情 | 详情 | |
| (V) | 61646 | methyl (1R,2S,3R,5S)-3-(3,4-dichlorophenyl)-8-oxabicyclo[3.2.1]octane-2-carboxylate | C15H16Cl2O3 | 详情 | 详情 | |
| (VI) | 61647 | [(1R,2R,3R,5S)-3-(3,4-dichlorophenyl)-8-oxabicyclo[3.2.1]oct-2-yl]methanol | C14H16Cl2O2 | 详情 | 详情 | |
| (VII) | 61648 | 4-PENTENOYL CHLORIDE | C5H7ClO | 详情 | 详情 |