(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanethioamide -Drug Synthesis Database

【结构式】

【分子编号】17121

【品名】(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanethioamide

【CA登记号】

【分子式】C₁₃H₁₄F₂N₄OS

【分子量】312.3433264

【元素组成】C 49.99% H 4.52% F 12.17% N 17.94% O 5.12% S 10.27%

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)

ER-30346 is synthesized by thiazole ring formation of (2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)thiobutanamide (I) and 4-bromoacetylbenzonitrile (II) by means of reflux in methanol. The thioamide (I) is obtained with excellent yield from a chiral nitrile (III) by heating with diethyl dithiophosphate in aqueous medium.

参考文献中间体

合成目标

【1】 Saji, I.; Tamoto, K.; Tanaka, Y.; Fujimoto, K.; Ohashi, N.; Stereoselective synthesis of antifungal agent threo-2-(2,4-difluorophenyl)-3-methylsulfonyl-1-(1H-1,2,4-triazol-1-yl)-2-butanol (SM-8668). Bull Chem Soc Jpn 1994, 67, 1427-33.
【2】 Konos, T.; Miyaoka, T.; Tajima, Y.; Oida, S.; Triazole antifungals. III. Stereocontrolled synthesis of an optically active triazolylmethyloxirane precursor to antifungal oxazolodine derivatives. Chem Pharm Bull 1991, 39, 9, 2241.
【3】 Tasaka, A.; Tamura, N.; Matsushita, Y.; Teranishi, K.; Hayashi, R.; Okonogi, K.; Itoh, K.; Optically active antifungal azoles. I. Synthesis and antifungal activity of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol and stereoisomers. Chem Pharm Bull 1993, 41, 6, 1035-42.
【4】 Naito, T.; Hata, K.; Tsuruoka, A.; ER-30346. Drugs Fut 1996, 21, 1, 20.
【5】 Naito, T.; Hata, K.; Kaku, Y.; Tsuruoka, A.; Tsukada, I.; Yanagisawa, M.; Toyosawa, T.; Nara, K. (Eisai Co., Ltd.); Azole antifungal agents, process for the preparation thereof and intermediates. CA 2141731; EP 0667346; JP 1995223950; JP 1996020578; JP 1996053426; US 5648372; US 5789429; US 5792781 .

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)	17121	(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanethioamide		C₁₃H₁₄F₂N₄OS	详情	详情
(II)	17122	4-(2-bromoacetyl)benzonitrile; 4-Cyanophenacyl bromide	20099-89-2	C₉H₆BrNO	详情	详情
(III)	17123	(2S,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanenitrile		C₁₃H₁₂F₂N₄O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Addition of trimethylsilyl cyanide to the known epoxide (I) produced the hydroxy nitrile (II). This was converted to the thioamide (III) upon treatment with diethyl dithiophosphate. Condensation between thioamide (III) and thiadiazolyl thiobenzamide (IV) in the presence of iodine furnished the target thiadiazole derivative.

参考文献中间体

合成目标

【1】 Fujii, T.; Tsukuda, T.; Shimma, N.; Komiyama, S.; Parallel synthesis of azole antifungals and identification of novel thiadiazole-containing antifungals. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 175.
【2】 Shimma, N.; Tsukuda, T.; Komiyama, S. (Basilea Pharmaceutica AG); Azole derivs.. US 6319933; WO 0179196 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	13114	1-[[(2S,3S)-2-(2,4-Difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole	C₁₂H₁₁F₂N₃O	详情	详情
(II)	17123	(2S,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanenitrile	C₁₃H₁₂F₂N₄O	详情	详情
(III)	17121	(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanethioamide	C₁₃H₁₄F₂N₄OS	详情	详情
(IV)	58588	4-(1,2,3-Thiadiazol-4-yl)thiobenzamide	C₉H₇N₃S₂	详情	详情

Extended Information