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【结 构 式】

【分子编号】55922

【品名】(1R)-1-[2-(2,5-difluorophenyl)-2-oxiranyl]ethyl tetrahydro-2H-pyran-2-yl ether; 2-({(1R)-1-[2-(2,5-difluorophenyl)-2-oxiranyl]ethyl}oxy)tetrahydro-2H-pyran

【CA登记号】

【 分 子 式 】C15H18F2O3

【 分 子 量 】284.3029264

【元素组成】C 63.37% H 6.38% F 13.36% O 16.88%

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:(IV)

Addition of 2,5-difluorophenylmagnesium bromide (I) to the O-tetrahydropyranyl lactic acid amide (II) afforded the propiophenone derivative (III). Oxirane (IV) was then obtained by reaction of ketone (III) with the sulfur ylide generated from trimethylsulfoxonium iodide and either NaH or BuLi. Epoxide ring opening with the sodium salt of 1,2,4-triazole (V) led to the triazolyl alcohol (VI) as a mixture of diastereoisomers. After acid hydrolysis of the tetrahydropyranyl protecting group of (VI), the resultant mixture of diols was separated by column chromatography. The desired (R,R) diastereoisomer (VII) was converted to epoxide (IX) via formation of mesylate (VIII), which was subsequently cyclized in the presence of NaOMe. Nitrile (X) was then obtained by reaction of oxirane (IX) with either trimethylsilyl cyanide, followed by desilylation with Bu4NF, or with acetone cyanohydrin and LiH. Conversion of nitrile (X) into thioamide (XI) was accomplished by treatment with diethyl dithiophosphate. Cyclization of thioamide (XI) with 4-cyanophenacyl bromide (XII) gave rise to the thiazole derivative (XIII).

1 Yamazaki, T.; Sakai, T.; Shimma, N.; Umeda, I.; Ichihara, S.; Ohwada, J.; Hayase, T.; Isshiki, Y.; Liu, P.; Tsukazaki, M. (F. Hoffmann-La Roche AG); 3-[4-(4-Cyanophenyl)thiazol-2-yl)]-1-(1H-1,2,4-triazol-1-yl)-butan-2-ol derivs. having antifungal activity. US 6300353; WO 9945008 .
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) 55920 bromo(2,5-difluorophenyl)magnesium C6H3BrF2Mg 详情 详情
(II) 45574 (2R)-1-(4-morpholinyl)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanone C12H21NO4 详情 详情
(III) 55921 (2R)-1-(2,5-difluorophenyl)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanone C14H16F2O3 详情 详情
(IV) 55922 (1R)-1-[2-(2,5-difluorophenyl)-2-oxiranyl]ethyl tetrahydro-2H-pyran-2-yl ether; 2-({(1R)-1-[2-(2,5-difluorophenyl)-2-oxiranyl]ethyl}oxy)tetrahydro-2H-pyran C15H18F2O3 详情 详情
(V) 13135 1H-1,2,4-Triazole; 1,2,4-Triazole 288-88-0 C2H3N3 详情 详情
(VI) 55923 (3R)-2-(2,5-difluorophenyl)-3-(tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanol C17H21F2N3O3 详情 详情
(VII) 55924 (2R,3R)-2-(2,5-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol C12H13F2N3O2 详情 详情
(VIII) 55925 (1R,2R)-2-(2,5-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl methanesulfonate C13H15F2N3O4S 详情 详情
(IX) 55926 1-{[(2S,3R)-2-(2,5-difluorophenyl)-3-methyloxiranyl]methyl}-1H-1,2,4-triazole C12H11F2N3O 详情 详情
(X) 55927 (2S,3R)-3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanenitrile C13H12F2N4O 详情 详情
(XI) 55928 (2R,3R)-3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanethioamide C13H14F2N4OS 详情 详情
(XII) 17122 4-(2-bromoacetyl)benzonitrile; 4-Cyanophenacyl bromide 20099-89-2 C9H6BrNO 详情 详情
(XIII) 55929 4-{2-[(1R,2R)-2-(2,5-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-1,3-thiazol-4-yl}benzonitrile C22H17F2N5OS 详情 详情
Extended Information