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【结 构 式】

【分子编号】20261

【品名】S-(2-pyridinyl) (2S)-2-methyl-3-(trityloxy)propanethioate

【CA登记号】

【 分 子 式 】C28H25NO2S

【 分 子 量 】439.57804

【元素组成】C 76.51% H 5.73% N 3.19% O 7.28% S 7.29%

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:(V)

The synthesis of (2S,3S)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1,2,4-triazol-1-yl)butyronitrile (XV), a key intermediate the synthesis of ER-30346 has been described: The tritylation of 3-hydroxy-2(S)-methylpropionic acid methyl ester (I) with trityl chloride in hot pyridine gives the trityl ether (II), which is hydrolyzed with LiOH in H2O/THF/methanol yielding the free acid (III). The esterification of (III) with 2-mercaptopyridine (IV) by means of dicyclohexylcarbodiimide (DCC) in dichloromethane gives the thioester (V), which is treated with 2,4-difluorophenylmagnesium bromide (VI) in THF yielding the propiophenone (VII), which by treatment with methyltriphenylphosphonium bromide/NaH in THF is converted into the methylene derivative (VIII). The oxidation of (VIII) with OsO4 and N-methylmorpholine oxide in acetone affords, after column chromatography, the chiral diol (IX), which is monomesylated with mesyl chloride/triethylamine in dichlormethane giving the monoester (X). The reaction of (X) with 1,2,4-triazol (XI) and NaH in DMF yields (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-1-(1,2,4-triazol-1-yl)-4-(triphenylmethoxy)-2-butanol (XII), which is detritylated with p-toluenesulfonic acid in methanol affording the diol (XIII). The oxidation of (XIII) with oxalyl chloride/DMSO in dichloromethane gives the aldehyde (XIV), which is finally treated with hydroxylamine-O-sulfonic acid in water yielding the desired bytyronitrile intermediate (XV) already referenced.

1 Kaku, Y.; et al.; A novel route for chiral synthesis of the triazole antifungal ER-30346. Chem Pharm Bull 1998, 46, 7, 1125.
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) 17128 Methyl (2S)-3-hydroxy-2-methylpropanoate 72657-23-9 C5H10O3 详情 详情
(II) 17129 Methyl (2S)-2-methyl-3-(trityloxy)propanoate C24H24O3 详情 详情
(III) 20259 (2S)-2-methyl-3-(trityloxy)propionic acid C23H22O3 详情 详情
(IV) 20260 2-Mercaptopyiridine; 2-pyridinethiol; 2-pyridinylhydrosulfide 2637-34-5 C5H5NS 详情 详情
(V) 20261 S-(2-pyridinyl) (2S)-2-methyl-3-(trityloxy)propanethioate C28H25NO2S 详情 详情
(VI) 20262 bromo(2,4-difluorophenyl)magnesium C6H3BrF2Mg 详情 详情
(VII) 17130 (2S)-1-(2,4-difluorophenyl)-2-methyl-3-(trityloxy)-1-propanone C29H24F2O2 详情 详情
(VIII) 17131 (2R)-3-(2,4-difluorophenyl)-2-methyl-3-butenyl trityl ether; 2,4-difluoro-1-[1-[(1R)-1-methyl-2-(trityloxy)ethyl]vinyl]benzene C30H26F2O 详情 详情
(IX) 17132 (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-4-(trityloxy)-1,2-butanediol C30H28F2O3 详情 详情
(X) 20266 (2R,3S)-2-(2,4-difluorophenyl)-2-hydroxy-3-methyl-4-(trityloxy)butyl methanesulfonate C31H30F2O5S 详情 详情
(XI) 13135 1H-1,2,4-Triazole; 1,2,4-Triazole 288-88-0 C2H3N3 详情 详情
(XII) 17135 (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-1-(1H-1,2,4-triazol-1-yl)-4-(trityloxy)-2-butanol C32H29F2N3O2 详情 详情
(XIII) 17136 (2S,3R)-3-(2,4-difluorophenyl)-2-methyl-4-(1H-1,2,4-triazol-1-yl)-1,3-butanediol C13H15F2N3O2 详情 详情
(XIV) 17137 (2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanal C13H13F2N3O2 详情 详情
(XV) 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
Extended Information