{(3aR,5R,6R,6aR)-6-hydroxy-2,2-dimethyl-6-[2-(trimethylsilyl)ethynyl]tetrahydrofuro[2,3-d][1,3]dioxol-5-yl}methyl 4-chlorobenzoate -Drug Synthesis Database

【结构式】

【分子编号】61575

【品名】{(3aR,5R,6R,6aR)-6-hydroxy-2,2-dimethyl-6-[2-(trimethylsilyl)ethynyl]tetrahydrofuro[2,3-d][1,3]dioxol-5-yl}methyl 4-chlorobenzoate

【CA登记号】

【分子式】C₂₀H₂₅ClO₆Si

【分子量】424.9531

【元素组成】C 56.53% H 5.93% Cl 8.34% O 22.59% Si 6.61%

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 reaction of 1,2-O-isopropylidene-D-xylofuranose (I) with 4-chlorobenzoyl chloride (II) and TEA gives the 5-O-(4-chlorobenzoate) (III), which is oxidized with TEMPO and NaClO to yield the 3-oxo derivative (IV). The ethynylation of (IV) by means of trimethylsilylethynyl magnesium bromide (V) affords the 3-C-trimethylsilylethynyl derivative (VI), which is hydrolyzed by means of refluxing aqueous HCOOH to provide the 3-C-ethynylated sugar (VII). The acylation of (VII) by means of 4-chlorobenzoyl chloride (II), TEA and DMAP gives the tetrabenzoate sugar (VIII), which is used for the glycosylation of bis trimethylsilyl cytosine (IX) by means of SnCl4 to yield the protected precursor (X). Finally, this compound is desilylated and debenzoylated by means of DBU in hot methanol to afford the target nucleoside.

参考文献中间体

合成目标

【1】 Nomura, M.; Sato, T.; Masato, W.; Tanaka, M.; Asao, T.; Shuto, S.; Matsuda, A.; Nucleosides and nucleotides. Part 212: Practical large-scale synthesis of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd), a potent antitumor nucleoside. Isobutyryloxy group as an efficient anomeric leaving group in the Vorbruggen glycosylation . Tetrahedron 2002, 58, 7, 1279.

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)	10295	p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride	122-01-0	C₇H₄Cl₂O	详情	详情
(III)	61573	[(3aR,5R,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl 4-chlorobenzoate		C₁₅H₁₇ClO₆	详情	详情
(IV)	61574	[(3aR,5R,6aS)-2,2-dimethyl-6-oxotetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl 4-chlorobenzoate		C₁₅H₁₅ClO₆	详情	详情
(V)	34561	methyl 3-methyl-1-(2-methylphenyl)-2-(trimethylsilyl)-1H-pyrrolo[3,2-c]quinolin-6-yl ether; 6-methoxy-3-methyl-1-(2-methylphenyl)-2-(trimethylsilyl)-1H-pyrrolo[3,2-c]quinoline		C₂₃H₂₆N₂OSi	详情	详情
(VI)	61575	{(3aR,5R,6R,6aR)-6-hydroxy-2,2-dimethyl-6-[2-(trimethylsilyl)ethynyl]tetrahydrofuro[2,3-d][1,3]dioxol-5-yl}methyl 4-chlorobenzoate		C₂₀H₂₅ClO₆Si	详情	详情
(VII)	61576	{(2R,3S,4R)-3,4,5-trihydroxy-3-[2-(trimethylsilyl)ethynyl]tetrahydro-2-furanyl}methyl 4-chlorobenzoate		C₁₇H₂₁ClO₆Si	详情	详情
(VIII)	61577	(3R,4R,5R)-3,4-bis[(4-chlorobenzoyl)oxy]-5-{[(4-chlorobenzoyl)oxy]methyl}-4-[2-(trimethylsilyl)ethynyl]tetrahydro-2-furanyl 4-chlorobenzoate		C₃₈H₃₀Cl₄O₉Si	详情	详情
(IX)	61578	N-(trimethylsilyl)-2-[(trimethylsilyl)oxy]-4-pyrimidinamine; N-(trimethylsilyl)-N-{2-[(trimethylsilyl)oxy]-4-pyrimidinyl}amine		C₁₀H₂₁N₃OSi₂	详情	详情
(X)	61579	(2R,3R,4R,5R)-4-[(4-chlorobenzoyl)oxy]-5-{[(4-chlorobenzoyl)oxy]methyl}-2-[2-oxo-4-[(trimethylsilyl)amino]-1(2H)-pyrimidinyl]-4-[2-(trimethylsilyl)ethynyl]tetrahydro-3-furanyl 4-chlorobenzoate		C₃₈H₃₈Cl₃N₃O₈Si₂	详情	详情

Extended Information