(2S,4R)-4-(2,4-difluorophenyl)-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]-5-(1H-1,2,4-triazol-1-yl)-1,4-pentanediol -Drug Synthesis Database

【结构式】

【分子编号】34842

【品名】(2S,4R)-4-(2,4-difluorophenyl)-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]-5-(1H-1,2,4-triazol-1-yl)-1,4-pentanediol

【CA登记号】

【分子式】C₁₉H₂₅F₂N₃O₄

【分子量】397.4221264

【元素组成】C 57.42% H 6.34% F 9.56% N 10.57% O 16.1%

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：(XVI)

Triol (XI) was enantioselectively acetylated to the (R)-monoacetate ester (XIV) employing EtOAc and porcine pancreatic lipase. Protection of the primary hydroxyl group of (XIV) with dihydropyran produced the tetrahydropyranyl ether (XV). After hydrolysis of the acetate ester of (XV) with KOH, tosylation of the resulting alcohol (XVI) furnished (XVII), which was subsequently cyclized to the cis tetrahydrofuran derivative (XVIII) in the presence of NaH. Acid deprotection of the tetrahydropyranyl ether of (XVIII) gave alcohol (XIX), which was then converted to tosylate (XIII).

参考文献中间体

合成目标

【1】 Saksena, A.K.; Girijavallabhan, V.M.; Lovey, R.G.; Pike, R.E.; Wang, H.; Liu, Y.-T.; Ganguly, A.K.; Bennett, F. (Schering Corp.); Tetrahydrofuran antifungals. EP 0773941; WO 9638443 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XI)	16332	(4R)-4-(2,4-difluorophenyl)-2-(hydroxymethyl)-5-(1H-1,2,4-triazol-1-yl)-1,4-pentanediol	C₁₄H₁₇F₂N₃O₃	详情	详情
(XIII)	16311	[(3S,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methyl 4-methylbenzenesulfonate	C₂₁H₂₁F₂N₃O₄S	详情	详情
(XIV)	34840	(2R,4R)-4-(2,4-difluorophenyl)-4-hydroxy-2-(hydroxymethyl)-5-(1H-1,2,4-triazol-1-yl)pentyl acetate	C₁₆H₁₉F₂N₃O₄	详情	详情
(XV)	34841	(2R,4R)-4-(2,4-difluorophenyl)-4-hydroxy-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]-5-(1H-1,2,4-triazol-1-yl)pentyl acetate	C₂₁H₂₇F₂N₃O₅	详情	详情
(XVI)	34842	(2S,4R)-4-(2,4-difluorophenyl)-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]-5-(1H-1,2,4-triazol-1-yl)-1,4-pentanediol	C₁₉H₂₅F₂N₃O₄	详情	详情
(XVII)	34843	(2R,4R)-4-(2,4-difluorophenyl)-4-hydroxy-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]-5-(1H-1,2,4-triazol-1-yl)pentyl 4-methylbenzenesulfonate	C₂₆H₃₁F₂N₃O₆S	详情	详情
(XVIII)	34844	[(3S,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methyl tetrahydro-2H-pyran-2-yl ether; 1-([(2R,4S)-2-(2,4-difluorophenyl)-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]tetrahydro-2-furanyl]methyl)-1H-1,2,4-triazole	C₁₉H₂₃F₂N₃O₃	详情	详情
(XIX)	16343	[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methanol	C₁₄H₁₅F₂N₃O₂	详情	详情

Extended Information