[(2R,3S,4R,5R)-5-[4-amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl]-3-(benzoyloxy)-4-iodotetrahydro-2-furanyl]methyl benzoate -Drug Synthesis Database

【结构式】

【分子编号】56704

【品名】[(2R,3S,4R,5R)-5-[4-amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl]-3-(benzoyloxy)-4-iodotetrahydro-2-furanyl]methyl benzoate

【CA登记号】

【分子式】C₂₃H₁₉FIN₃O₆

【分子量】579.3233532

【元素组成】C 47.69% H 3.31% F 3.28% I 21.91% N 7.25% O 16.57%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VI)

The acylation of 2,3-O-isopropylidene-alpha-D-xylofuranose (I) with benzoyl chloride and pyridine gives the dibenzoyl ester (II), which is deprotected by means of H2SO4/HOAc in hot THF to yield 3,5-di-O-benzoyl-alpha-D-xylofuranose (III). The reaction of (III) with PPh3, I2 and imidazole in dichloromethane affords the glycal (IV), which is used in the glycosylation of the N,O-disilylated 5-fluorocytosine (V) by means of NIS in dichloromethane to provide the 2'-alpha-iodonucleoside (VI). The treatment of (VI) with Zn in EtOH/ethyl acetate (HOAc is used as catalyst) gives the unsaturated nucleoside (VII), which is finally debenzoylated by means of butylamine in THF.

参考文献中间体

合成目标

【1】 Chen, S.-H.; Lin, S.; King, I.; Spinka, T.; Dutschman, G.E.; Gullen, E.A.; Cheng, Y.-C.; Doyle, T.W.; Synthesis and comparative evaluation of two antiviral agents: beta-L-Fd4C and beta-D-Fd4C. Bioorg Med Chem Lett 1998, 8, 22, 3245.

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)	41907	(3aR,5R,6S,6aR)-5-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol	20031-21-4	C₈H₁₄O₅	详情	详情
(II)	56701	[(3aR,5R,6S,6aR)-6-(benzoyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzoate		C₂₂H₂₂O₇	详情	详情
(III)	56702	[(2R,3R,4R,5S)-3-(benzoyloxy)-4,5-dihydroxytetrahydro-2-furanyl]methyl benzoate		C₁₉H₁₈O₇	详情	详情
(IV)	56703	[(2R,3R)-3-(benzoyloxy)-2,3-dihydro-2-furanyl]methyl benzoate		C₁₉H₁₆O₅	详情	详情
(V)	36959	5-fluoro-N-(trimethylsilyl)-2-[(trimethylsilyl)oxy]-4-pyrimidinamine; N-[5-fluoro-2-[(trimethylsilyl)oxy]-4-pyrimidinyl]-N-(trimethylsilyl)amine		C₁₀H₂₀FN₃OSi₂	详情	详情
(VI)	56704	[(2R,3S,4R,5R)-5-[4-amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl]-3-(benzoyloxy)-4-iodotetrahydro-2-furanyl]methyl benzoate		C₂₃H₁₉FIN₃O₆	详情	详情
(VII)	56705	{(2S,5R)-5-[4-amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl]-2,5-dihydro-2-furanyl}methyl benzoate		C₁₆H₁₄FN₃O₄	详情	详情

Extended Information