【结 构 式】 |
【药物名称】Tecadenoson , CVT-510 【化学名称】N6-[3(R)-Tetrahydrofuranyl]adenosine 【CA登记号】204512-90-3, 204512-92-5 ((S)-isomer), 343921-68-6 (deleted CAS), 204512-89-0 (undefined isomer) 【 分 子 式 】C14H19N5O5 【 分 子 量 】337.33803 |
【开发单位】CV Therapeutics (Originator) 【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Adenosine A1 Agonists |
合成路线1
The reaction of 3-tetrahydrofuroic acid (I) with diphenyl phosphoryl azide (DPPA) in refluxing dioxane gave the intermediate isocyanate (II), which was treated with benzyl alcohol (III) to yield carbamate (IV). Subsequent hydrogenolysis in the presence of Pd/C afforded racemic amine (V), which was resolved by treatment with S-(+)-10-camphorsulfonyl chloride (VI) in pyridine, followed by column chromatography and recrystallization from acetone of the resulting sulfonamide (VII). Then, hydrolysis in HCl-AcOH provided the S-amine (VIII). Condensation of amine (VIII) with 6-chloropurine riboside (IX) in the presence of triethylamine in refluxing MeOH furnished the title compound.
【1】 Sorbera, L.A.; Bayes, M.; Castañer, J.; Martín, L.; Tecadenoson. Drugs Fut 2002, 27, 9, 846. |
【2】 Lum, R.T.; Pfister, J.R.; Schow, S.R.; Wick, M.M.; Nelson, M.G.; Schreiner, G.F. (CV Therapeutics, Inc.); N6 Heterocyclic substd. adenosine derivs.. EP 0920438; EP 0992510; JP 2000501426; US 5789416; WO 9808855 . |
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) | 18708 | tetrahydro-3-furancarboxylic acid | 89364-31-8 | C5H8O3 | 详情 | 详情 |
(II) | 18709 | tetrahydro-3-furanyl isocyanate; 3-isocyanatotetrahydrofuran | C5H7NO2 | 详情 | 详情 | |
(III) | 18710 | Benzyl alcohol; Phenylmethanol | 100-51-6 | C7H8O | 详情 | 详情 |
(IV) | 18711 | benzyl tetrahydro-3-furanylcarbamate | C12H15NO3 | 详情 | 详情 | |
(V) | 18712 | tetrahydro-3-furanylamine; tetrahydro-3-furanamine | C4H9NO | 详情 | 详情 | |
(VI) | 18713 | (7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonyl chloride | C10H15ClO3S | 详情 | 详情 | |
(VII) | 18714 | (7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)-N-[(3S)tetrahydro-3-furanyl]methanesulfonamide | C14H23NO4S | 详情 | 详情 | |
(VIII) | 18715 | (3S)tetrahydro-3-furanamine; (3S)tetrahydro-3-furanylamine | C4H9NO | 详情 | 详情 | |
(IX) | 18716 | 6-chloropurine riboside; (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 2004-06-0 | C10H11ClN4O4 | 详情 | 详情 |