Desciclovir, Deoxyacyclovir, BW-A-515-U, A-515U, -Drug Synthesis Database

【结构式】

【药物名称】Desciclovir, Deoxyacyclovir, BW-A-515-U, A-515U

【化学名称】2-[(2-Amino-9H-purin-9-yl)methoxy]ethanol

【CA登记号】84408-37-7

【分子式】C₈H₁₁N₅O₂

【分子量】209.20917

【开发单位】GlaxoSmithKline (Originator)

【药理作用】ANTIINFECTIVE THERAPY, Antiviral Drugs

合成路线1 合成路线2

合成路线1

A new synthesis of A-515-U has been reported. The compound can be synthesized in two similar ways: 1) The reaction of 9-(2-acetoxyethoxymethyl)-2-(acetylamino)-6,9-dihydro-1H-purin-6-one (I) with POCl3 and 2,4,6-trimethylpyridine in refluxing acetonitrile gives 9-(2-acetoxyethoxymethyl)-2-(acetylamino)-6-chloro-9H-purine (II), which is dechlorinated with formic acid - triethylamine and Pd/C in refluxing acetone, yielding 9-(2-acetoxyethoxymethyl)-2-(acetylamino)-9H-purine (III). Finally, this compound is deacetylated in water. 2) Purine (I) is partially deacetylated with triethylamine in refluxing ethanol to give 9-(2-acetoxyethoxymethyl)-2-amino-6,9-dihydro-1H-purin-6-one (IV), which is treated with POCl3 as before to yield the chloropurine (V). The dechlorination of (V) with HCO2H as before or with ammonium formate - Pd/C affords 9-(2-acetoxyethoxymethyl)-2-amino-9H-purine (VI), which is finally deacetylated with methylamine as before.

参考文献中间体

【1】 Stimac, A.; Kobe, J.; A new synthesis of acyclovir prodrugs. N2-Acetylacyclovir and 6-deoxya cyclovir. Synthesis 1990, 6, 6, 461-4.

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)	10784	2-[[2-(acetamido)-6-oxo-1,6-dihydro-9H-purin-9-yl]methoxy]ethyl acetate; Acetic acid 2-(2-acetamido-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-ethyl ester	75128-73-3	C₁₂H₁₅N₅O₅	详情	详情
(II)	10785	2-[[2-(acetamido)-6-chloro-9H-purin-9-yl]methoxy]ethyl acetate		C₁₂H₁₄ClN₅O₄	详情	详情
(III)	10786	2-[[2-(acetamido)-9H-purin-9-yl]methoxy]ethyl acetate		C₁₂H₁₅N₅O₄	详情	详情
(IV)	10787	2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]ethyl acetate		C₁₀H₁₃N₅O₄	详情	详情
(V)	10788	2-[(2-amino-6-chloro-9H-purin-9-yl)methoxy]ethyl acetate		C₁₀H₁₂ClN₅O₃	详情	详情
(VI)	10789	2-[(2-amino-9H-purin-9-yl)methoxy]ethyl acetate		C₁₀H₁₃N₅O₃	详情	详情

合成路线2

The condensation of 2-amino 6 chloropurine (I) with 2-benzyioxyethoxymethyl chloride (II), by means of K2CO3 in DMF gives 2-amino-6 chloro 9-(2 benzyloxyethoxymethyl)purine (III), which is then dechlorinated by reduction with H2 over Pd/C in ethanol containing triethylamine.

参考文献中间体

【1】 Beauchamp, L.M.; Krenitsky, T.A.; Schaeffer, H.J. (Glaxo Wellcome plc); Antiviral purine derivs.. EP 0108285; EP 0158847; ES 8603482; GB 2151222; US 4609662; US 4649140 .
【2】 Schaeffer, H.J. (Glaxo Wellcome plc); Purine derivs.. US 4294831 .
【3】 Castaner, J.; Hopkins, S.J.; A-515-U. Drugs Fut 1986, 11, 2, 92.

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)	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
(II)	24092	1-[[2-(chloromethoxy)ethoxy]methyl]benzene		C₁₀H₁₃ClO₂	详情	详情
(III)	24093	9-[[2-(benzyloxy)ethoxy]methyl]-6-chloro-9H-purin-2-ylamine		C₁₅H₁₆ClN₅O₂	详情	详情

Extended Information