• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】35523

【品名】2-[2-(benzyloxy)ethyl]-1,3-propanediol

【CA登记号】

【 分 子 式 】C12H18O3

【 分 子 量 】210.27312

【元素组成】C 68.55% H 8.63% O 22.83%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(I)

Treatment of diol (I) with 1,1'-carbonyldiimidazole produced the cyclic carbonate (II). Cleavage of the O-benzyl group of (II) by hydrogenolysis over Pd/C, gave alcohol (III), which was converted to mesylate (IV) by means of MsCl and Et3N. Subsequent coupling of (IV) with 2-amino-6-chloropurine (V) produced the 9-alkylated derivative (VI). The chlorine atom of (VI) was then removed by hydrogenolysis in the presence of Pd/C and Et3N to furnish (VII). Finally, opening of the cyclic carbonate group of (VII) with isopropanol upon heating in the presence of silica gel yielded the target compound.

1 Kim, D.-K.; Lee, N.; Kim, Y.-W.; Chang, K.; Kim, J.S.; Im, G.J.; Choi, W.S.; Jung, I.; Kim, T.S.; Hwang, Y.Y.; Min, D.S.; Um, K.A.; Cho, Y.B.; Kim, K.H.; Synthesis and evaluation of 2-amino-9-(3-hydroxymethyl-4-alkoxycarbonyloxybut-1-yl)purines as potential prodrugs of penciclovir. J Med Chem 1998, 41, 18, 3435.
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) 35523 2-[2-(benzyloxy)ethyl]-1,3-propanediol C12H18O3 详情 详情
(II) 35524 5-[2-(benzyloxy)ethyl]-1,3-dioxan-2-one C13H16O4 详情 详情
(III) 35525 5-(2-hydroxyethyl)-1,3-dioxan-2-one C6H10O4 详情 详情
(IV) 35526 2-(2-oxo-1,3-dioxan-5-yl)ethyl methanesulfonate C7H12O6S 详情 详情
(V) 11644 6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine 10310-21-1 C5H4ClN5 详情 详情
(VI) 35534 5-[2-(2-amino-6-chloro-9H-purin-9-yl)ethyl]-1,3-dioxan-2-one C11H12ClN5O3 详情 详情
(VII) 35527 5-[2-(2-amino-9H-purin-9-yl)ethyl]-1,3-dioxan-2-one C11H13N5O3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

The reaction of monolabeled diethyl malonate (I) with 2-benzyloxyethyl bromide (II) by means of NaH in refluxing THF gives the corresponding benzyloxyethyl derivative (III), which is reduced with LiAlH4 in ethyl ether yielding the diol (IV). The protection of (IV) by reaction with 2,2-dimethoxypropane (V) and p-toluenesulfonic acid affords the 1,3-dioxane (VI), which is debenzylated with H2 over Pd/C in THF giving the alcohol (VII). The reaction of (VII) with CBr4 and PPh3 in DMF yields the bromide (VIII), which is condensed with the purine (IX) by means of K2CO3 in DMF affording the expected purin-9-yl derivative (X). The hydrolysis of the 1,3-dioxane group with AcOH /water gives the diol (XI), which is monoacylated with isopropyl chloroformate (XII) by means of cool pyridine yielding the mixture of regioisomers (XIII), (XIV). Finally, this mixture is dechlorinated with ammonium formate over Pd/C in refluxing methanol afffording the target compound also as a mixture of regioisomers.

1 Kim, D.K.; et al.; Synthesis of carbon-14 labelled 2-amino-9-(3-hydroxymethyl-4-isopropoxycarbonyloxybut-1-yl)purine (SK 1875), a potential prodrug of penciclovir. J Label Compd Radiopharm 1999, 42, 6, 597.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VII),(VIII) 10916 2-(2,2-Dimethyl-1,3-dioxan-5-yl)-1-ethanol C8H16O3 详情 详情
(XIII),(XIV) 35533 4-(2-amino-6-chloro-9H-purin-9-yl)-2-(hydroxymethyl)butyl isopropyl carbonate C14H20ClN5O4 详情 详情
(I) 16829 Diethyl malonate 105-53-3 C7H12O4 详情 详情
(I) 45348 diethyl malonate C7H12O4 详情 详情
(II) 35528 1-[(2-bromoethoxy)methyl]benzene; benzyl 2-bromoethyl ether 1462-37-9 C9H11BrO 详情 详情
(III) 35529 diethyl 2-[2-(benzyloxy)ethyl]malonate C16H22O5 详情 详情
(III) 45349 diethyl 2-[2-(benzyloxy)ethyl]malonate C16H22O5 详情 详情
(IV) 35523 2-[2-(benzyloxy)ethyl]-1,3-propanediol C12H18O3 详情 详情
(IV) 45350 2-[2-(benzyloxy)ethyl]-1,3-propanediol C12H18O3 详情 详情
(V) 10722 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane 77-76-9 C5H12O2 详情 详情
(VI) 35530 5-[2-(benzyloxy)ethyl]-2,2-dimethyl-1,3-dioxane; benzyl 2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl ether C15H22O3 详情 详情
(VI) 45351 5-[2-(benzyloxy)ethyl]-2,2-dimethyl-1,3-dioxane; benzyl 2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl ether C15H22O3 详情 详情
(VII) 45352 2-(2,2-dimethyl-1,3-dioxan-5-yl)-1-ethanol C8H16O3 详情 详情
(VIII) 45353 2-(2,2-dimethyl-1,3-dioxan-5-yl)-1-ethanol C8H16O3 详情 详情
(IX) 11644 6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine 10310-21-1 C5H4ClN5 详情 详情
(X) 35531 6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-ylamine; 6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-amine C13H18ClN5O2 详情 详情
(X) 45354 6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-amine; 6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-ylamine C13H18ClN5O2 详情 详情
(XI) 35532 2-[2-(2-amino-6-chloro-9H-purin-9-yl)ethyl]-1,3-propanediol C10H14ClN5O2 详情 详情
(XI) 45355 2-[2-(2-amino-6-chloro-9H-purin-9-yl)ethyl]-1,3-propanediol C10H14ClN5O2 详情 详情
(XII) 26492 2-[(chlorocarbonyl)oxy]propane 108-23-6 C4H7ClO2 详情 详情
(XIII) 45356 4-(2-amino-6-chloro-9H-purin-9-yl)-2-(hydroxymethyl)butyl isopropyl carbonate C14H20ClN5O4 详情 详情
(XIV) 45357 4-(2-amino-6-chloro-9H-purin-9-yl)-2-(hydroxymethyl)butyl isopropyl carbonate C14H20ClN5O4 详情 详情
Extended Information