【结 构 式】 |
【分子编号】60203 【品名】8-[4-(hydroxymethyl)bicyclo[2.2.2]oct-1-yl]-1,3-dipropyl-3,9-dihydro-1H-purine-2,6-dione 【CA登记号】 |
【 分 子 式 】C20H30N4O3 【 分 子 量 】374.48336 【元素组成】C 64.15% H 8.07% N 14.96% O 12.82% |
合成路线1
该中间体在本合成路线中的序号:(V)The cyclization of 5,6-diamino-1,3-dipropylpyrimidine-2,4(1H,3H)-dione (I) with bicyclo[2,2,2]octane-1,4-dicarboxylic acid monoethyl ester (II) by means of HATU and TEA in acetonitrile gives the dipropylxanthine derivative (III), which is esterified with MeOH and sulfuric acid, yielding the methyl ester (IV). The reduction of the ester group of (IV) by means of LiBH4 in refluxing THF affords the hydroxymethyl derivative (V), which is oxidized with DMP in dichloromethane to provide the carbaldehyde (VI). The condensation of aldehyde (VI) with phosphonate (VII) by means of KHMDS in toluene leads to the acrylic acid methyl ester (VIII), which is hydrolyzed with LiOH in methanol/water to give the free acid (IX). Finally the double bond of the acrylic moiety is hydrogenated with H2 over Pd/C in methanol to yield the target xanthine derivative.
【1】 Ensinger, C.L.; Kumaravel, G.; Petter, R.C.; Dowling, J.E.; Kiesman, W.F.; Chang, H.X.; Lin, K.C. (Biogen, Inc.); Polycycloalkylpurines as adenosine receptor antagonists. EP 1230243; JP 2003513982; WO 0134610 . |
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) | 14628 | 5,6-diamino-1,3-dipropyl-2,4(1H,3H)-pyrimidinedione | C10H18N4O2 | 详情 | 详情 | |
(II) | 60200 | 4-[(propyloxy)carbonyl]bicyclo[2.2.2]octane-1-carboxylic acid | C13H20O4 | 详情 | 详情 | |
(III) | 60201 | 4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)bicyclo[2.2.2]octane-1-carboxylic acid | C20H28N4O4 | 详情 | 详情 | |
(IV) | 60202 | methyl 4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)bicyclo[2.2.2]octane-1-carboxylate | C21H30N4O4 | 详情 | 详情 | |
(V) | 60203 | 8-[4-(hydroxymethyl)bicyclo[2.2.2]oct-1-yl]-1,3-dipropyl-3,9-dihydro-1H-purine-2,6-dione | C20H30N4O3 | 详情 | 详情 | |
(VI) | 60204 | 4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)bicyclo[2.2.2]octane-1-carbaldehyde | C20H28N4O3 | 详情 | 详情 | |
(VII) | 13272 | Methyl 2-(dimethoxyphosphoryl)acetate; Trimethyl phosphoroacetate | 5927-18-4 | C5H11O5P | 详情 | 详情 |
(VIII) | 60205 | methyl 3-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)bicyclo[2.2.2]oct-1-yl]-2-propenoate | C23H32N4O4 | 详情 | 详情 | |
(IX) | 60206 | 3-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)bicyclo[2.2.2]oct-1-yl]-2-propenoic acid | C22H30N4O4 | 详情 | 详情 |