2-[[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]sulfanyl]-1,3-propanediol -Drug Synthesis Database

【结构式】

【分子编号】41338

【品名】2-[[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]sulfanyl]-1,3-propanediol

【CA登记号】

【分子式】C₁₅H₁₉F₂N₃O₃S

【分子量】359.3970864

【元素组成】C 50.13% H 5.33% F 10.57% N 11.69% O 13.36% S 8.92%

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：(XI)

Displacement of tosylate (VII) with sodium thioacetate afforded thioester (VIII) (1). Hydrolysis of the thioester (VIII) in the presence of NaOMe, followed by condensation of the intermediate thiol with the chiral epoxide (IX) furnished the mercapto alcohol (X). Hydrolysis of the cyclic acetal of (X) in methanolic HCl gave triol (XI). This was finally condensed with aldehyde (VI) in the presence of p-TsOH and molecular sieves to yield the title compound.

参考文献中间体

合成目标

【1】 Oida, S.; et al.; Synthesis and antifungal activity of R-102557, a novel dioxane-triazole compound. 19th Symp Med Chem (Nov 17 1999, Tokyo) 1999, Abst 2P-15.
【2】 Tajima, Y.; Oida, S.; Konosu, T.; et al.; Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives. Chem Pharm Bull 2000, 48, 5, 694.
【3】 Oida, S.; Tanaka, T.; Tajima, Y.; Konosu, T.; Somada, A.; Miyaoka, T.; Yasuda, H. (Sankyo Co., Ltd.); Triazole antifungal agent. EP 0841327; JP 1996333350; US 5977152; WO 9631491 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	41334	(2E,4E)-5-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-pentadienal	C₁₄H₁₂F₄O₂	详情	详情
(VII)	41335	2-phenyl-1,3-dioxan-5-yl 4-methylbenzenesulfonate	C₁₇H₁₈O₅S	详情	详情
(VIII)	41336	S-(2-phenyl-1,3-dioxan-5-yl) ethanethioate	C₁₂H₁₄O₃S	详情	详情
(IX)	31738	1-[[(2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole	C₁₂H₁₁F₂N₃O	详情	详情
(X)	41337	(2R,3R)-2-(2,4-difluorophenyl)-3-[(2-phenyl-1,3-dioxan-5-yl)sulfanyl]-1-(1H-1,2,4-triazol-1-yl)-2-butanol	C₂₂H₂₃F₂N₃O₃S	详情	详情
(XI)	41338	2-[[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]sulfanyl]-1,3-propanediol	C₁₅H₁₉F₂N₃O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Addition of the thiol liberated from thioester (VII) in the presence of NaOMe to the chiral epoxide (VIII) afforded thioether (IX). Acid hydrolysis of the acetal function of (IX) yielded diol (X). Then, acetalization of diol (IX) with aldehyde (XI) furnished the title compound.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; del Fresno, M.; Rabasseda, X.; CS-758. Drugs Fut 2003, 28, 3, 217.
【2】 Nakamura, Y.; Konosu, T.; Oida, S.; et al.; Synthesis and in vitro antifungal activities of novel triazole antifungal agent CS-758. Chem Pharm Bull 2001, 49, 12, 1647.
【4】 Tajima, Y.; Oida, S.; Konosu, T.; et al.; Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives. Chem Pharm Bull 2000, 48, 5, 694.
【5】 Oida, S.; Tanaka, T.; Tajima, Y.; Konosu, T.; Somada, A.; Miyaoka, T.; Yasuda, H. (Sankyo Co., Ltd.); Triazole antifungal agent. EP 0841327; JP 1996333350; US 5977152; WO 9631491 .
【6】 Mori, M.; Oida, S.; Uchida, T.; Nakagawa, A.; Kounosu, T.; Ohya, T. (Sankyo Co., Ltd.); Triazole antifungal agents. JP 2002161035 .
【3】 Oida, S.; Mori, M.; nakamura, Y.; Habuki, S.; Kuwahara, S.; Somada, A.; Harada, Y.; Uchida, T.; Konosu, T.; R-120758, a novel triazole antifungal agent: Synthesis and structure-activity relationship. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1087.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	45515	3-fluoro-4-[(1E,3E)-5-oxo-1,3-pentadienyl]benzonitrile	C₁₂H₈FNO	详情	详情
(VII)	41336	S-(2-phenyl-1,3-dioxan-5-yl) ethanethioate	C₁₂H₁₄O₃S	详情	详情
(VIII)	13114	1-[[(2S,3S)-2-(2,4-Difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole	C₁₂H₁₁F₂N₃O	详情	详情
(IX)	41337	(2R,3R)-2-(2,4-difluorophenyl)-3-[(2-phenyl-1,3-dioxan-5-yl)sulfanyl]-1-(1H-1,2,4-triazol-1-yl)-2-butanol	C₂₂H₂₃F₂N₃O₃S	详情	详情
(X)	41338	2-[[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]sulfanyl]-1,3-propanediol	C₁₅H₁₉F₂N₃O₃S	详情	详情

Extended Information