[(2S,5R)-5-(6-Amino-9H-purin-9-yl)-2,5-dihydro-2-furanyl]methanol -Drug Synthesis Database

【结构式】

【分子编号】11994

【品名】[(2S,5R)-5-(6-Amino-9H-purin-9-yl)-2,5-dihydro-2-furanyl]methanol

【CA登记号】7057-48-9

【分子式】C₁₀H₁₁N₅O₂

【分子量】233.22984

【元素组成】C 51.5% H 4.75% N 30.03% O 13.72%

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：(VII)

This compound is prepared by two related ways: 1) The partial silylation of adenosine (I) with tert-butyldimethylsilyl chloride and imidazole gives 5'-O-(tert-butyldimethylsilyl)adenosine (II), which by reaction with 1,1'-thiocarbonyldiimidazole (III) in hot DMF is converted into 5'-O-(tert-butyldimethylsilyl)-2',3'-O-thionocarbonyladenosine (IV). The desulfurization of (IV) with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine (V) or triethyl phosphite in THF yields 5'-O-(tert-butyldimethylsilyl)-2',3'-didehydro-2',3'-dideoxyadenosine (VI), which is deprotected with tetrabutylammonium fluoride in THF affording 2',3'-didehydro-2',3'-dideoxyadenosine (VII). Finally, this compound is hydrogenated with H2 over Pd/C in methanol. 2) The reaction of silylated adenosine (II) with CS2 and NaOH in DMSO, followed by methylation with methyl iodide gives 5'-O-(tert-butyldimethylsilyl)-2',3'-bis-O-[(methylthio)thiocarbonyl]ad enosine (VIII), which is desulfurized with tributyltin hydride and AIBN in refluxing toluene to yield the dideoxy-didehydroadenosine (VI), already obtained.

参考文献中间体

合成目标

【1】 Chu, C.K.; Bhadti, V.S.; Doboszewski, B.; Gu, Z.P.; Kosugi, Y.; Pullaiah, K.C.; Van Roey, P.; General syntheses of 2',3'-dideoxynucleosides and 2',3'-didehydro-2',3'-dideoxynucleosides. J Org Chem 1989, 54, 2217-25.

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)	11988	Adenosine; (2R,3R,4S,5R)-2-(6-Amino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol	58-61-7	C₁₀H₁₃N₅O₄	详情	详情
(II)	11989	(2R,3R,4S,5R)-2-(6-Amino-9H-purin-9-yl)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)tetrahydro-3,4-furandiol		C₁₆H₂₇N₅O₄Si	详情	详情
(III)	11990	Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole	6160-65-2	C₇H₆N₄S	详情	详情
(IV)	11991	(3aR,4R,6R,6aR)-4-(6-Amino-9H-purin-9-yl)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)tetrahydrofuro[3,4-d][1,3]dioxole-2-thione		C₁₇H₂₅N₅O₄SSi	详情	详情
(V)	11992	1,3-Dimethyl-2-phenyl-1,3,2-diazaphospholane; 1,3-DIMETHYL-2-PHENYL-1,3,2-DIAZAPHOSPHOLIDINE 1,3-Dimethy?2-phenyl-1,3,2-diazaphospholidine	22429-12-5	C₁₀H₁₅N₂P	详情	详情
(VI)	11993	9-[(2R,5S)-5-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-2,5-dihydro-2-furanyl]-9H-purin-6-ylamine; 9-[(2R,5S)-5-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-2,5-dihydro-2-furanyl]-9H-purin-6-amine		C₁₆H₂₅N₅O₂Si	详情	详情
(VII)	11994	[(2S,5R)-5-(6-Amino-9H-purin-9-yl)-2,5-dihydro-2-furanyl]methanol	7057-48-9	C₁₀H₁₁N₅O₂	详情	详情
(VIII)	11995	O-((2R,3R,4R,5R)-2-(6-Amino-9H-purin-9-yl)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-[[(methylsulfanyl)carbothioyl]oxy]tetrahydro-3-furanyl) S-methyl carbonodithioate		C₂₀H₃₁N₅O₄S₄Si	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 elimination reaction of (III) with sodium ethoxide in DMF gives 2',3'-dideoxy-2',3'-didehydroadenosine (V), which is hydrogenated with H2 over Pd/C in ethanol.

参考文献中间体

合成目标

【1】 McCarthy, J.R.; et al.; Purine nucleosides. XIV. Unsaturated furanosyl adenine nucleosides prepared via base-catalysed elimination reactions of 2'-deoxyadenosine derivatives. J Am Chem Soc 1966, 88, 7, 1549-53.
【2】 Castaner, J.; Hopkins, S.J.; Serradell, M.N.; Blancafort, P.; 2',3'-Dideoxyadenosine. Drugs Fut 1982, 7, 4, 244.

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)	34204	(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-[(trityloxy)methyl]tetrahydro-3-furanol		C₂₉H₂₇N₅O₃	详情	详情
(II)	36381	(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-[(trityloxy)methyl]tetrahydro-3-furanyl 4-methylbenzenesulfonate		C₃₆H₃₃N₅O₅S	详情	详情
(III)	36382	(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydro-3-furanyl 4-methylbenzenesulfonate		C₁₇H₁₉N₅O₅S	详情	详情
(V)	11994	[(2S,5R)-5-(6-Amino-9H-purin-9-yl)-2,5-dihydro-2-furanyl]methanol	7057-48-9	C₁₀H₁₁N₅O₂	详情	详情

Extended Information