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【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information