diethyl (2-hydroxyethoxy)methylphosphonate -Drug Synthesis Database

【结构式】

【分子编号】39884

【品名】diethyl (2-hydroxyethoxy)methylphosphonate

【CA登记号】

【分子式】C₇H₁₇O₅P

【分子量】212.182742

【元素组成】C 39.62% H 8.08% O 37.7% P 14.6%

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：(III)

PMEA was prepared by a straightforward route from readily available 2-acetoxyethoxymethyl chloride (I). The key intermediate, diethyl 2-bromoethylmethoxyphosphonate (IV), was coupled with adenine (V) in the presence of sodium hydride, followed by hydrolysis to afford PMEA.

参考文献中间体

合成目标

【1】 Hwang, J.-T.; Choi, J.-R.; Novel phosphonate nucleosides as antiviral agents. Drugs Fut 2004, 29, 2, 163.

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)	63950	2-(chloromethoxy)ethyl acetate		C₅H₉ClO₃	详情	详情
(II)	39883	2-[(diethoxyphosphoryl)methoxy]ethyl acetate		C₉H₁₉O₆P	详情	详情
(III)	39884	diethyl (2-hydroxyethoxy)methylphosphonate		C₇H₁₇O₅P	详情	详情
(IV)	39886	diethyl (2-bromoethoxy)methylphosphonate		C₇H₁₆BrO₄P	详情	详情
(V)	10343	9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine	73-24-5	C₅H₅N₅	详情	详情
(VI)	39673	diethyl [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonate		C₁₂H₂₀N₅O₄P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The 9-[2-(phosphonomethoxy)ethyl]adenine (VIII), intermediate in the synthesis of adefovir has been obtained as follows: 1) The partial hydrolysis of 2-acetoxyethoxymethylphosphonic acid diethyl ester (I) with Dowex 50XB in ethanol gives the corresponding 2-hydroxyethoxymethylphosphonate (II), which is treated with CCl4/PPh3, with CBr4/PPh3 or with TsCl yielding 2-choroethoxy (III), 2-bromoethoxy (IV) or 2-tosyloxyethoxy (V) derivatives, respectively (1). The condensation of (III), (IV) or (V) with adenine (VI) by means of NaH in hot DMF affords 9-[2-(diethoxyphosphorylmethoxy)ethyl]adenine (VII), which is finally treated with TMS-Br in acetonitrile to give the desired intermediate 9-[2-(phosphonomethoxy)ethyl]adenine (VIII). 2) The condensation of N6-benzoyl-9-(2-hydroxyethyl)adenine (IX) with tosyloxymethylphosphonic acid dimethyl ester (X) by means of NaH in warm DMF gives 9-[2-(dimethoxyphosphorylmethoxy)ethyl]adenine (X), which is treated first with NaOH in DMF/water and finally with TMS-I in DMF to afford the desired intermediate 9-[2-(phosphonomethoxy)ethyl]adenine (VIII).

参考文献中间体

合成目标

【1】 Rosenberg, I.; Holý, A.; Synhtesis of 9-(2-phosphonylmethoxyethyl)adenine and related compounds. Coll Czech Chem Commun 1987, 52, 2801.
【2】 Holý, A.; et al.; Synthesi of N-(2-phosphonylmethoxyethyl) derivatives of heterocyclic bases. Coll Czech Chem Commun 1989, 54, 2190.

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)	39883	2-[(diethoxyphosphoryl)methoxy]ethyl acetate		C₉H₁₉O₆P	详情	详情
(II)	39884	diethyl (2-hydroxyethoxy)methylphosphonate		C₇H₁₇O₅P	详情	详情
(III)	39885	diethyl (2-chloroethoxy)methylphosphonate		C₇H₁₆ClO₄P	详情	详情
(IV)	39886	diethyl (2-bromoethoxy)methylphosphonate		C₇H₁₆BrO₄P	详情	详情
(V)	39887	diethyl [2-[(4-methylphenyl)sulfonyl]ethoxy]methylphosphonate		C₁₄H₂₃O₆PS	详情	详情
(VI)	10343	9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine	73-24-5	C₅H₅N₅	详情	详情
(VII)	39673	diethyl [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonate		C₁₂H₂₀N₅O₄P	详情	详情
(VIII)	16165	[2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonic acid		C₈H₁₂N₅O₄P	详情	详情
(IX)	39888	N-[9-(2-hydroxyethyl)-9H-purin-6-yl]benzamide		C₁₄H₁₃N₅O₂	详情	详情
(X)	39889	(dimethoxyphosphoryl)methyl 4-methylbenzenesulfonate		C₁₀H₁₅O₆PS	详情	详情
(XI)	39890	dimethyl [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonate		C₁₀H₁₆N₅O₄P	详情	详情

Extended Information