【结 构 式】 |
【药物名称】CVT-2759 【化学名称】5'-O-(N-Methylcarbamoyl)-N6-[tetrahydrofuran-3(R)-yl]adenosine 【CA登记号】 【 分 子 式 】C16H22N6O6 【 分 子 量 】394.39034 |
【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 the chloropurine (I) with tetrahydrofuran-2(R)-amine (II) gives N6-(furan-2(R)-yl)adenosine (III), which is treated with 2,2-dimethoxypropane and Ts-OH in hot DMF to yield N6-(furan-2-(R)-yl)-2'O,3'O-isopropylideneadenosine (IV). The reaction of (IV) with CDI and methylamine in THF affords N6-(furan-2-(R)-yl)-2'O,3'O-isopropylidene-5'O-(N-methylcarbamoyl)adenosine (V), which is finally deprotected with HOAc in hot water to provide the target adenosine derivative.
【1】 Palle, V.P.; et al.; A1 adenosine receptor agonist- SAR of 5'-carbamates and 5'-thionocarbamates of N6-substituted adenosine derivatives. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 23. |
【2】 Belardinelli, L.; Zablocki, J.A.; Palle, V.P.; Ibrahim, P.N.; Varkhedkar, V. (CV Therapeutics, Inc.); N6 Heterocylic 5' modified adenosine derivs.. US 6258793; WO 0140244; WO 0140245 . |
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) | 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 |
(II) | 53578 | (3R)-tetrahydro-3-furanamine; (3R)-tetrahydro-3-furanylamine | n/a | C4H9NO | 详情 | 详情 |
(III) | 53575 | (2R,3S,4R,5R)-2-(hydroxymethyl)-5-{6-[(3R)tetrahydro-3-furanylamino]-9H-purin-9-yl}tetrahydro-3,4-furandiol | n/a | C14H19N5O5 | 详情 | 详情 |
(IV) | 53576 | ((3aR,4R,6R,6aS)-2,2-dimethyl-6-{6-[(3R)tetrahydro-3-furanylamino]-9H-purin-9-yl}tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol | n/a | C17H23N5O5 | 详情 | 详情 |
(V) | 53577 | ((3aR,4R,6R,6aS)-2,2-dimethyl-6-{6-[(3R)tetrahydro-3-furanylamino]-9H-purin-9-yl}tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl methylcarbamate | n/a | C19H26N6O6 | 详情 | 详情 |
Extended Information