(2R,3S,4R)-2-(hydroxymethyl)-5-methoxytetrahydro-3,4-furandiol -Drug Synthesis Database

【结构式】

【分子编号】41258

【品名】(2R,3S,4R)-2-(hydroxymethyl)-5-methoxytetrahydro-3,4-furandiol

【CA登记号】

【分子式】C₆H₁₂O₅

【分子量】164.15828

【元素组成】C 43.9% H 7.37% O 48.73%

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：(I)

The reaction of methyl D-ribofuranoside (I) with SOCl2 gives methyl 5-chloro-5-deoxy-2,3-O-sulfinyl-D-ribofuranoside (II), which is treated with ammonia to yield methyl 5-chloro-5-deoxy-D-ribofuranoside (III). The reaction of (IV) with benzoyl chloride and pyridine affords the dibenzoate (IV), which is treated with lithium azide in DMF to provide the 5'-azido derivative (V). The condensation of 3-iodo-1H-pyrazolo[3,4-d]pyrimidine-4-amine (VII) (prepared by iodination of (1H-pyrazolo[3,4-d]pyrimidine-4-amine (VI) with N-iodosuccinimide (NIS)) with the azido derivative (V) by means of BF3/Et in nitromethane gives the adduct (VIII), which is debenzoylated with sodium methoxide yielding the azido nucleoside (IX). Finally this compound is reduced with triphenylphosphine and ammonia to furnish the target 5'-amino-nucleoside.

参考文献中间体

合成目标

【1】 Cottam, H.B.; New adenosine kinase inhibitors with oral antiinflammatory activity. Drugs Fut 1994, 19, 5, 485.
【2】 Kasukhin, L.F.; Gololobov, Yu.G.; Zhmurova, I.N.; Sixty years of Staudinger reaction. Tetrahedron 1981, 37, 437-472.
【3】 Browne, C.E.; Ugarkar, B.G.; Mullane, K.M.; Gruber, H.E.; Bullough, D.A.; Erion, M.D.; Castellino, A. (Sicor Inc.); Adenosine kinase inhibitors. EP 0496617; JP 1993112595; WO 9212718 .

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)	41258	(2R,3S,4R)-2-(hydroxymethyl)-5-methoxytetrahydro-3,4-furandiol		C₆H₁₂O₅	详情	详情
(II)	41252	(4S)-4-(chloromethyl)-6-methoxytetrahydro-2lambda(4)-furo[3,4-d][1,3,2]dioxathiol-2-one		C₆H₉ClO₅S	详情	详情
(III)	41253	(2S,3S,4R)-2-(chloromethyl)-5-methoxytetrahydro-3,4-furandiol		C₆H₁₁ClO₄	详情	详情
(IV)	41254	(3R,4R,5S)-4-(benzoyloxy)-5-(chloromethyl)-2-methoxytetrahydro-3-furanyl benzoate		C₂₀H₁₉ClO₆	详情	详情
(V)	41255	(3R,4R,5R)-5-(azidomethyl)-4-(benzoyloxy)-2-methoxytetrahydro-3-furanyl benzoate		C₂₀H₁₉N₃O₆	详情	详情
(VI)	41249	4-amine-1H-pyrazolo[3,4-d]pyrimidine; 1H-pyrazolo[3,4-d]pyrimidin-4-ylamine; 1H-pyrazolo[3,4-d]pyrimidin-4-amine	2380-63-4	C₅H₅N₅	详情	详情
(VII)	41250	3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine; 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine		C₅H₄IN₅	详情	详情
(VIII)	41256	(2R,3R,4R,5R)-2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-5-(azidomethyl)-4-(benzoyloxy)tetrahydro-3-furanyl benzoate		C₂₄H₁₉IN₈O₅	详情	详情
(IX)	41257	(2R,3R,4S,5R)-2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-5-(azidomethyl)tetrahydro-3,4-furandiol		C₁₀H₁₁IN₈O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXI)

Methylation of D-ribose (XX) with MeOH using HCl yields methyl Dribofuranoside (XXI), which is then benzoylated with BzCl in CHCl3/pyr to give the protected intermediate (XXII). Bromination of methyl ether (XXII) with HBr in AcOH furnishes bromide (X). Acetylation of methyl ether (XXII) with Ac2O and AcOH produces acetate (XIV) .

参考文献中间体

合成目标

【1】 Recondo, E.F., Rinderknecht, H. Eine neue, einfache Synthese des 1-OAcetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranosides. Helv Chim Acta 1959, 42(4): 1171.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	33832	[(2R,3S,4R)-3,4-bis(benzoyloxy)-5-bromotetrahydro-2-furanyl]methyl benzoate		C₂₆H₂₁BrO₇	详情	详情
(XIV)	26984	(2R,3R,4R,5S)-5-(acetoxy)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate		C₂₈H₂₄O₉	详情	详情
(XX)	10016	D-Ribose; (3R,4S,5R)-5-(Hydroxymethyl)tetrahydro-2,3,4-furantriol; (2R,3R,4R)-2,3,4,5-Tetrahydroxypentanal	50-69-1	C₅H₁₀O₅	详情	详情
(XXI)	41258	(2R,3S,4R)-2-(hydroxymethyl)-5-methoxytetrahydro-3,4-furandiol		C₆H₁₂O₅	详情	详情
(XXII)	12247	[(2R,3R,4R)-3,4-bis(benzoyloxy)-5-methoxytetrahydro-2-furanyl]methyl benzoate		C₂₇H₂₄O₈	详情	详情

Extended Information