6-Chloro-6,9-dihydro-1H-purin-2-ylamine; 6-Chloro-6,9-dihydro-1H-purin-2-amine -Drug Synthesis Database

【结构式】

【分子编号】10913

【品名】6-Chloro-6,9-dihydro-1H-purin-2-ylamine; 6-Chloro-6,9-dihydro-1H-purin-2-amine

【CA登记号】

【分子式】C₅H₆ClN₅

【分子量】171.58904

【元素组成】C 35% H 3.52% Cl 20.66% N 40.81%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

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.

参考文献中间体

合成目标

【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	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：(IX)

The condensation of 6-chloroguanine (IX) with (V) by means of ammonium sulfate in refluxing HMDS gives 9-[[1,3-bis(benzyloxy)-2-propoxy]methyl]-6-chloroguanine (XI), which is treated with sodium methoxide and mercaptoethanol in refluxing methanol to yield 9-[[1,3-bisbenzyloxy)-2-propoxy]methyl]guanine (XI), which is finally deprotected by a treatment with palladium hydroxide in refluxing cyclohexane.

参考文献中间体

合成目标

【1】 Kennell, W.L.; Ogilvie, K.K.; Cheriyan, U.O.; Smith, K.O.; Radatus, B.K.; Galloway, K.S.; Biologically active acylnucleoside analogs. II. The synthesis of 9-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl]guanine (BIOLF-62). Can J Chem 1982, 60, 24, 3005.
【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	分子式	供应商	用于合成
(V)	29160	[2-(benzyloxy)-1-[(benzyloxy)methyl]ethoxy]methyl acetate	C₂₀H₂₄O₅	详情	详情
(IX)	10913	6-Chloro-6,9-dihydro-1H-purin-2-ylamine; 6-Chloro-6,9-dihydro-1H-purin-2-amine	C₅H₆ClN₅	详情	详情
(X)	29164	9-([2-(benzyloxy)-1-[(benzyloxy)methyl]ethoxy]methyl)-6-chloro-9H-purin-2-ylamine	C₂₃H₂₄ClN₅O₃	详情	详情
(XI)	29165	2-amino-9-([2-(benzyloxy)-1-[(benzyloxy)methyl]ethoxy]methyl)-1,9-dihydro-6H-purin-6-one	C₂₃H₂₅N₅O₄	详情	详情

Extended Information