(2R,3R,4S,5R)-2-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol -Drug Synthesis Database

【结构式】

【分子编号】22302

【品名】(2R,3R,4S,5R)-2-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol

【CA登记号】

【分子式】C₁₃H₁₉N₅O₄S

【分子量】341.39116

【元素组成】C 45.74% H 5.61% N 20.51% O 18.75% S 9.39%

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：(IV)

Diazotization of (I) with isoamyl nitrite in the presence of dipropyl disulfide afforded sulfide (III) through the intermediate diazonium salt (II). Further substitution of the chloro atom of (III) for ammonia provided 2-(propylthio)adenosine (IV). The 5'-hydroxyl group of (IV) was then phosphorylated by reaction with phosphoryl chloride in cold triethyl phosphate followed by aqueous work-up. The resulting 5'-monophosphate (V) was treated with carbonyl diimidazole and tri-n-butylamine to produce the phosphoryl imidazole intermediate (VI), which was finally condensed with dichloromethylenebis(phosphonic acid) (X). The target compound was isolated as the tetrasodium salt upon treatment with NaI in methanol-acetone.

参考文献中间体

合成目标

【1】 Ingall, A.H.; Dixon, J.; Bailey, A.; Coombs, M.E.; Cox, D.; McInally, J.I.; Hunt, S.F.; Kindon, N.D.; Teobald, B.J.; Willis, P.A.; Humphries, R.G.; Leff, P.; Clegg, J.A.; Smith, J.A.; Tomlinson, W.; Antagonists of the platelet P2T receptor: A novel approach to antithrombotic therapy. J Med Chem 1999, 42, 2, 213.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	22299	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2-amino-6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate	C₁₆H₁₈ClN₅O₇	详情	详情
(II)	22300	6-Chloro-9-(2'-O,3'-O,5'-O-Triacetyl-beta-D-ribofuranosyl)purine-2-diazonium cation	C₁₆H₁₈ClN₅O₇	详情	详情
(III)	22301	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[6-chloro-2-(propylsulfanyl)-9H-purin-9-yl]tetrahydro-3-furanyl acetate	C₁₉H₂₃ClN₄O₇S	详情	详情
(IV)	22302	(2R,3R,4S,5R)-2-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol	C₁₃H₁₉N₅O₄S	详情	详情
(V)	22303	[(2R,3S,4R,5R)-5-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydro-2-furanyl]methyl dihydrogen phosphate	C₁₃H₂₀N₅O₇PS	详情	详情
(VI)	22304	[(2R,3S,4R,5R)-5-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydro-2-furanyl]methyl hydrogen 1H-imidazol-1-ylphosphonate	C₁₆H₂₂N₇O₆PS	详情	详情
(X)	22305	dichloro(phosphono)methylphosphonic acid	CH₄Cl₂O₆P₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Alkylation of adenosine-2-thione (I) with iodopropane produced the propylthioether (II). Subsequent treatment with phosphoryl chloride in triethyl phosphate, followed by aqueous work-up afforded (propylthio)adenylic acid (III). Then, after activation with carbonyldiimidazole, the condensation of (III) with difluoromethylenebisphosphonic acid (IV) generated the target anhydride.

参考文献中间体

合成目标

【1】 Ingall, A.H.; Cage, P.A. (Celltech Medeva plc); ATP analogues. EP 0508687; US 5654285 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	28758	1-iodopropane	107-08-4	C₃H₇I	详情	详情
(I)	28113	6-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-3,9-dihydro-2H-purine-2-thione		C₁₀H₁₃N₅O₄S	详情	详情
(II)	22302	(2R,3R,4S,5R)-2-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol		C₁₃H₁₉N₅O₄S	详情	详情
(III)	22303	[(2R,3S,4R,5R)-5-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydro-2-furanyl]methyl dihydrogen phosphate		C₁₃H₂₀N₅O₇PS	详情	详情
(IV)	28114	difluoro(phosphono)methylphosphonic acid		CH₄F₂O₆P₂	详情	详情

Extended Information