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【结 构 式】 
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【分子编号】10910 【品名】2-(Hydroxymethyl)-1,4-butanediol 【CA登记号】 |
【 分 子 式 】C5H12O3 【 分 子 量 】120.14848 【元素组成】C 49.98% H 10.07% O 39.95% |
合成路线1
该中间体在本合成路线中的序号：(I)The synthesis of penciclovir by two related ways has been reported: 1) The reaction of 2-(hydroxymethyl)butane-1,4-diol (I) with formaldehyde (or an aldehyde such as trimethylacetaldehyde) (II) by means of H2SO4 (or p-toluenesulfonic acid, TsOH) gives the dioxane (III), which by reaction first with methanesulfonyl chloride and triethylamine and then with NaI in acetone affords the corresponding 5-(2-iodoethyl)-1,3-dioxane (IV). The reaction of (IV) with 2-amino-6-chloropurine (V) by means of K2CO3 in DMF gives the corresponding condensation product (VI), which is finally hydrolyzed and deprotected with refluxing 2M aqueous HCl. 2) The reaction of triol (I) with 2,2-dimethoxypropane (VII) by means of TsOH gives the corresponding 1,3-dioxane (VIII), which by reaction with triphenylphosphine and CBr4 is converted to the 5-(2-bromoethyl) derivative (IX). The reaction of (IX) with the purine (V) by means of K2CO3 as before affords the corresponding condensation product (X), which is hydrolyzed and deprotected with 2M HCl as before.
| 【1】 Grinter, T.J.; Choudary, B.M.; MacBeath, F.S.; Parratt, M.J.; Geen, G.R.; Influence of remote structure upon regioselectivity in the N-alkylation of 2-amino-6-chloropurine: Application to the synthesis of penciclovir. Nucleosides Nucleotides 1994, 13, 4, 979. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IIIa) | 10911 | 2-(1,3-Dioxan-5-yl)-1-ethanol | C6H12O3 | 详情 | 详情 | |
| (IVa) | 10912 | 5-(2-Iodoethyl)-1,3-dioxane | C6H11IO2 | 详情 | 详情 | |
| (VIa) | 10914 | 6-Chloro-9-[2-(1,3-dioxan-5-yl)ethyl]-6,9-dihydro-1H-purin-2-amine; 6-Chloro-9-[2-(1,3-dioxan-5-yl)ethyl]-6,9-dihydro-1H-purin-2-ylamine | C11H16ClN5O2 | 详情 | 详情 | |
| (I) | 10910 | 2-(Hydroxymethyl)-1,4-butanediol | C5H12O3 | 详情 | 详情 | |
| (V) | 10913 | 6-Chloro-6,9-dihydro-1H-purin-2-ylamine; 6-Chloro-6,9-dihydro-1H-purin-2-amine | C5H6ClN5 | 详情 | 详情 | |
| (VII) | 10915 | 3,3-Dimethyl-2,4-pentanedione | C7H12O2 | 详情 | 详情 | |
| (VIII) | 10916 | 2-(2,2-Dimethyl-1,3-dioxan-5-yl)-1-ethanol | C8H16O3 | 详情 | 详情 | |
| (IX) | 10917 | 5-(2-Bromoethyl)-2,2-dimethyl-1,3-dioxane | C8H15BrO2 | 详情 | 详情 | |
| (X) | 10918 | 6-Chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-6,9-dihydro-1H-purin-2-ylamine; 6-Chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-6,9-dihydro-1H-purin-2-amine | C13H20ClN5O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Treatment of 4-(2,2-dimethyl-1-oxopropyl)benzoic acid (I) with thionyl chloride afforded the corresponding acid chloride (II). The title triester was then obtained by acylation of 2-(hydroxymethyl)-1,4-butanediol (IV) with acid chloride (II) in the presence of DMAP or Et3N. The triol (IV) has been obtained by reduction of ethane-1,1,2-tricarboxylic acid triethyl ester (III) with LiAlH4 under standard conditions.
| 【1】 Otero, D.A.; Bebernitz, G.R.; Dain, J.G.; Strohschein, R.J.; Deems, R.O.; Simpson, W.R.; Reduction in glucose levels in STZ diabetic rats by 4-(2,2-dimethyl-1-oxopropyl)benzoic acid: A prodrug approach for targeting the liver. J Med Chem 2001, 44, 4, 512. |