2-(2,2-Dimethyl-1,3-dioxan-5-yl)-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】10916

【品名】2-(2,2-Dimethyl-1,3-dioxan-5-yl)-1-ethanol

【CA登记号】

【分子式】C₈H₁₆O₃

【分子量】160.21324

【元素组成】C 59.98% H 10.07% O 29.96%

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：(VIII)

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：(VII),(VIII)

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.

参考文献中间体

合成目标

【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