2-[[2-(acetamido)-6-oxo-1,6-dihydro-9H-purin-9-yl]methoxy]-3-(acetoxy)propyl acetate -Drug Synthesis Database

【结构式】

【分子编号】29170

【品名】2-[[2-(acetamido)-6-oxo-1,6-dihydro-9H-purin-9-yl]methoxy]-3-(acetoxy)propyl acetate

【CA登记号】

【分子式】C₁₅H₁₉N₅O₇

【分子量】381.34536

【元素组成】C 47.24% H 5.02% N 18.36% O 29.37%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XV)

The acetylation of 4-hydroxymethyl-1,3-dioxolane (XII) gives the corresponding acetate (XIII), which by reaction with acetic anhydride and ZnCl2 is converted to 1,3-diacetoxy-2-(acetoxymethoxy)propane (XIV). The condensation of (XIV) with diacetylguanine (VI) by means of ethanesulfonic acid (B) yields the triacetoxy precursor (XV), which is hydrolyzed with aqueous methylamine.

参考文献中间体

合成目标

【1】 Field, A.K.; Tolman, R.L.; Ashton, W.A.; Karkas, J.D.; Activation by thymidine kinase and potent antiherpetic activity of 2'-nor-2'-deoxyguanosine (2'NDG). Biochem Biophys Res Commun 1982, 108, 4, 1716.
【2】 Galloway, K.S.; Radatus, B.K.; Kennell, W.L.; Smith, K.O.; Ogilvie, K.K.; A new nucleoside analog, 9-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl]guanine, highly active in vitro aganist herpes simplex virus types 1 and 2. Antimicrob Agents Chemother 1982, 22, 1, 55-61.
【3】 Pento, J.T.; Serradell, M.N.; Castaner, J.; BIOLF-62. Drugs Fut 1985, 10, 5, 365.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	19273	acetyl chloride	75-36-5	C₂H₃ClO	详情	详情
(B)	29169	1-ethanesulfonic acid	594-45-6	C₂H₆O₃S	详情	详情
(VI)	29161	N-(9-acetyl-6-oxo-6,9-dihydro-1H-purin-2-yl)acetamide; N2,9-Diacetylguanine	3056-33-5	C₉H₉N₅O₃	详情	详情
(XII)	29166	1,3-dioxolan-4-ylmethanol	4740-78-7	C₄H₈O₃	详情	详情
(XIII)	29167	1,3-dioxolan-4-ylmethyl acetate		C₆H₁₀O₄	详情	详情
(XIV)	29168	3-(acetoxy)-2-[(acetoxy)methoxy]propyl acetate		C₁₀H₁₆O₇	详情	详情
(XV)	29170	2-[[2-(acetamido)-6-oxo-1,6-dihydro-9H-purin-9-yl]methoxy]-3-(acetoxy)propyl acetate		C₁₅H₁₉N₅O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The reaction of 4-(chloromethyl)-1,3-dioxolane (I) with Ac2O, HOAc and ZnCl2 gives the diacetoxy compound (II), which is treated with KOAc to yield the triacetoxy compound (III). The condensation of (III) with diacetyl guanine (IV) by means of ethylsulfonic acid affords the triacetyl ganciclovir (V), which is finally deacetylated with methylamine in methanol.

参考文献中间体

合成目标

【1】 Gao, H.; Mitra, A.K.; Synthesis of acyclovir, ganciclovir and their prodrugs: A review. Synthesis 2000, 3, 329.

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)	46049	4-(chloromethyl)-1,3-dioxolane		C₄H₇ClO₂	详情	详情
(II)	46050	[2-(acetoxy)-1-(chloromethyl)ethoxy]methyl acetate		C₈H₁₃ClO₅	详情	详情
(III)	46051	3-(acetoxy)-2-(2-oxopropoxy)propyl acetate		C₁₀H₁₆O₆	详情	详情
(IV)	29151	5H-dibenzo[a,d]cyclohepten-5-one; Dibenzosuberenone	2222-33-5	C₁₅H₁₀O	详情	详情
(V)	29170	2-[[2-(acetamido)-6-oxo-1,6-dihydro-9H-purin-9-yl]methoxy]-3-(acetoxy)propyl acetate		C₁₅H₁₉N₅O₇	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

The condensation of diacetyl guanine (I) with 1,3-diacetoxy-2-(acetoxymethoxy)propane (II) by means of TsOH in hot DMF gives the target intermediate, N2-acetyl-9-[2-acetoxy-1-(acetoxymethyl)ethoxymethyl]guanine (III). (see Synthline Scheme no. 11147104a, intermediate no. (XV)).

参考文献中间体

合成目标

【1】 Kumar, Y.; Khanduri, C.H.; Ray, P.C.; Babu, J.S. (Ranbaxy Laboratories Ltd.); A process for the preparation of ganciclovir intermediate N2-acetyl-9-(1,3-diacetoxy-2-propoxymethyl)guanine. WO 0333498 .

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)	29161	N-(9-acetyl-6-oxo-6,9-dihydro-1H-purin-2-yl)acetamide; N2,9-Diacetylguanine	3056-33-5	C₉H₉N₅O₃	详情	详情
(II)	64100	2-(acetyloxy)-1-[(acetyloxy)methyl]ethyl acetate		C₉H₁₄O₆	详情	详情
(III)	29170	2-[[2-(acetamido)-6-oxo-1,6-dihydro-9H-purin-9-yl]methoxy]-3-(acetoxy)propyl acetate		C₁₅H₁₉N₅O₇	详情	详情

Extended Information