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【结 构 式】 
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【分子编号】43514 【品名】2-[(1R,2S)-2-(2,4-difluorophenyl)-2-hydroxy-3-[isopropoxy(dimethyl)silyl]-1-methylpropyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one 【CA登记号】 |
【 分 子 式 】C26H31F6N3O4Si 【 分 子 量 】591.6258792 【元素组成】C 52.78% H 5.28% F 19.27% N 7.1% O 10.82% Si 4.75% |
合成路线1
该中间体在本合成路线中的序号：(XXVIII)Compound (XIII) can follow two different routes for its conversion into the intermediate product (XXIV): i) Reaction of (XIII) with vinylmagnesium bromide (XXI) in THF provides vinyl derivative (XXII), which is then converted into aldehyde (XXIII) by ozonolysis, followed by addition of dimethylsulfide (DMS). Reduction of aldehyde (XXIII) by means of NaBH4 in MeOH affords alcohol (XXIV). Conversion of (XXII) into (XXIV) can also be achieved by first treatment with NaIO4 and OsO4 in MeOH/H2O followed by reduction with NaBH4 in MeOH. ii) Treatment of (XIII) with (dimethylisopropoxysilyl)-methylmagnesium chloride (XXVII) in THF provides derivative (XXVIII), which is then converted into (XXIV) by treatment with H2O2/NaHCO3 in MeOH-THF. Final conversion of (XXIV) into the target product is achieved by first mesylation of (XXIV) by means of MsCl and Et3N in EtOAc to yield mesylated derivative (XXV), followed by its reaction with 1H-1,2,4-triazole in DMF in the presence of K2CO3.
| 【1】 Kitazaki, T.; et al.; Optically active antifungal azoles. IX. An alternative synthetic route for 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone and its analogs. Chem Pharm Bull 1999, 47, 3, 360. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 43507 | 2-[(1R)-2-(2,4-difluorophenyl)-1-methyl-2-oxoethyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C20H15F6N3O3 | 详情 | 详情 | |
| (XXI) | 16524 | bromo(vinyl)magnesium | 1826-67-1 | C2H3BrMg | 详情 | 详情 |
| (XXII) | 43513 | 2-[(1R,2S)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-butenyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C22H19F6N3O3 | 详情 | 详情 | |
| (XXIII) | 43515 | (2S,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[5-oxo-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl]butanal | C21H17F6N3O4 | 详情 | 详情 | |
| (XXIV) | 43516 | 2-[(1R,2S)-2-(2,4-difluorophenyl)-2,3-dihydroxy-1-methylpropyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C21H19F6N3O4 | 详情 | 详情 | |
| (XXV) | 43517 | 2-((1R,2S)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]propyl)-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C24H25F6N3O4S | 详情 | 详情 | |
| (XXVI) | 13135 | 1H-1,2,4-Triazole; 1,2,4-Triazole | 288-88-0 | C2H3N3 | 详情 | 详情 |
| (XXVII) | 43512 | chloro[[isopropoxy(dimethyl)silyl]methyl]magnesium | C6H15ClMgOSi | 详情 | 详情 | |
| (XXVIII) | 43514 | 2-[(1R,2S)-2-(2,4-difluorophenyl)-2-hydroxy-3-[isopropoxy(dimethyl)silyl]-1-methylpropyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C26H31F6N3O4Si | 详情 | 详情 |