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【结 构 式】 
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【分子编号】22303 【品名】[(2R,3S,4R,5R)-5-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydro-2-furanyl]methyl dihydrogen phosphate 【CA登记号】 |
【 分 子 式 】C13H20N5O7PS 【 分 子 量 】421.371062 【元素组成】C 37.06% H 4.78% N 16.62% O 26.58% P 7.35% S 7.61% |
合成路线1
该中间体在本合成路线中的序号：(V)Diazotization of (I) with isoamyl nitrite in the presence of dipropyl disulfide afforded sulfide (III) through the intermediate diazonium salt (II). Further substitution of the chloro atom of (III) for ammonia provided 2-(propylthio)adenosine (IV). The 5'-hydroxyl group of (IV) was then phosphorylated by reaction with phosphoryl chloride in cold triethyl phosphate followed by aqueous work-up. The resulting 5'-monophosphate (V) was treated with carbonyl diimidazole and tri-n-butylamine to produce the phosphoryl imidazole intermediate (VI), which was finally condensed with dichloromethylenebis(phosphonic acid) (X). The target compound was isolated as the tetrasodium salt upon treatment with NaI in methanol-acetone.
| 【1】 Ingall, A.H.; Dixon, J.; Bailey, A.; Coombs, M.E.; Cox, D.; McInally, J.I.; Hunt, S.F.; Kindon, N.D.; Teobald, B.J.; Willis, P.A.; Humphries, R.G.; Leff, P.; Clegg, J.A.; Smith, J.A.; Tomlinson, W.; Antagonists of the platelet P2T receptor: A novel approach to antithrombotic therapy. J Med Chem 1999, 42, 2, 213. |
| 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) | 22299 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2-amino-6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H18ClN5O7 | 详情 | 详情 | |
| (II) | 22300 | 6-Chloro-9-(2'-O,3'-O,5'-O-Triacetyl-beta-D-ribofuranosyl)purine-2-diazonium cation | C16H18ClN5O7 | 详情 | 详情 | |
| (III) | 22301 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[6-chloro-2-(propylsulfanyl)-9H-purin-9-yl]tetrahydro-3-furanyl acetate | C19H23ClN4O7S | 详情 | 详情 | |
| (IV) | 22302 | (2R,3R,4S,5R)-2-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C13H19N5O4S | 详情 | 详情 | |
| (V) | 22303 | [(2R,3S,4R,5R)-5-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydro-2-furanyl]methyl dihydrogen phosphate | C13H20N5O7PS | 详情 | 详情 | |
| (VI) | 22304 | [(2R,3S,4R,5R)-5-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydro-2-furanyl]methyl hydrogen 1H-imidazol-1-ylphosphonate | C16H22N7O6PS | 详情 | 详情 | |
| (X) | 22305 | dichloro(phosphono)methylphosphonic acid | CH4Cl2O6P2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Alkylation of adenosine-2-thione (I) with iodopropane produced the propylthioether (II). Subsequent treatment with phosphoryl chloride in triethyl phosphate, followed by aqueous work-up afforded (propylthio)adenylic acid (III). Then, after activation with carbonyldiimidazole, the condensation of (III) with difluoromethylenebisphosphonic acid (IV) generated the target anhydride.
| 【1】 Ingall, A.H.; Cage, P.A. (Celltech Medeva plc); ATP analogues. EP 0508687; US 5654285 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 28758 | 1-iodopropane | 107-08-4 | C3H7I | 详情 | 详情 | |
| (I) | 28113 | 6-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-3,9-dihydro-2H-purine-2-thione | C10H13N5O4S | 详情 | 详情 | |
| (II) | 22302 | (2R,3R,4S,5R)-2-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C13H19N5O4S | 详情 | 详情 | |
| (III) | 22303 | [(2R,3S,4R,5R)-5-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydro-2-furanyl]methyl dihydrogen phosphate | C13H20N5O7PS | 详情 | 详情 | |
| (IV) | 28114 | difluoro(phosphono)methylphosphonic acid | CH4F2O6P2 | 详情 | 详情 |