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【结 构 式】

【药物名称】Ifoxetine sulfate(Rec INNM), CGP-15210G

【化学名称】(±)-Bis[cis-3-hydroxy-4-(2,3-dimethylphenoxy)piperidine] sulfate

【CA登记号】66208-11-5 (free base)

【 分 子 式 】C26H40N2O8S

【 分 子 量 】540.6813

【开发单位】Novartis (Originator)

【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS

合成路线1

Reaction of the N-carbobenzyloxy-protected tetrahydropyridine derivative (I) with m-chloroperbenzoic acid (MCPBA) in ethylene chloride gives the stable oily epoxide (II), which, upon treatment with 2,3-dimethyphenol in acetonitrile in the presence of aqueous NaOH, affords the crystalline trans-3 hydroxy-4-phenoxy derivative (III). Oxidation of this aicohol to the corresponding ketone (IV) is best achieved by means of DMSO reagents, in particular DMSO and pyridine-SO3 adduct. Treatment of the ketone (IV) with potassium tri-sec-butylborohydride (K-Selectride(R)) in THF yields the cis-3-hydroxy-4-phenoxy derivative (V) in a highly stereoselective reaction. Hydrogenation of (V) with H2 over Pd/C in ethanol and subsequent salt formation with aqueous H2SO4 leads to racemic, diastereomerically pure CGP-l5210 G.

1 Paioni, R.; et al.; CGP 15 210 G, an unusual inhibitor of serotonin (5-HT) uptake. VIIIth Intl Symp Med Chem (Aug 27-31, Uppsala) 1985, 2, 130.
2 Paioni, R. (Novartis AG); Derivs. of perhydro-aza-heterocycles. DE 2738477; US 4160837 .
3 Waldmeier, P.C.; Paioni, R.; Delini-Stula, A.; Ifoxetine sulfate. Drugs Fut 1987, 12, 2, 126.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
40074 2,3-dimethylphenol 526-75-0 C8H10O 详情 详情
(I) 22854 benzyl 3,6-dihydro-1(2H)-pyridinecarboxylate C13H15NO2 详情 详情
(II) 22855 benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate C13H15NO3 详情 详情
(III) 22856 benzyl (3R,4R)-4-(2,3-dimethylphenoxy)-3-hydroxy-1-piperidinecarboxylate C21H25NO4 详情 详情
(IV) 22857 benzyl (4R)-4-(2,3-dimethylphenoxy)-3-oxo-1-piperidinecarboxylate C21H23NO4 详情 详情
(V) 22858 benzyl (3S,4R)-4-(2,3-dimethylphenoxy)-3-hydroxy-1-piperidinecarboxylate C21H25NO4 详情 详情
Extended Information