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【结 构 式】 
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【分子编号】20309 【品名】tert-butyl 4-(4-[5-oxo-1-[4-(trifluoromethoxy)benzyl]-1,5-dihydro-4H-1,2,4-triazol-4-yl]phenyl)-1-piperazinecarboxylate 【CA登记号】 |
【 分 子 式 】C25H28F3N5O4 【 分 子 量 】519.5238296 【元素组成】C 57.8% H 5.43% F 10.97% N 13.48% O 12.32% |
合成路线1
该中间体在本合成路线中的序号：(XI)1) The reaction of 1-(4-nitrophenyl)piperazine (I) with tert-butyl dicarbonate (II) and triethylamine in dichloromethane gives 4-(4-nitrophenyl)piperazine-1-carboxylic acid tert-butyl ester (III), which is reduced with H2 over Pd/C, yielding the corresponding 4-amino compound (IV). The reaction of (IV) with phenyl chloroformate (V) and triethylamine in dichloromethane affords the carbamate (VI), which by reaction with hydrazine is converted into the semicarbazide (VII). The cyclization of (VII) with formamidine (VIII) and triethylamine in hot 2-methoxyethanol affords the triazolone (IX), which is condensed with 4-(trifluoromethoxy)benzyl bromide (X) by means of Cs2CO3 in DMF, giving the disubstituted triazolone (XI). The deprotection, elimination of the tert-butoxycarbonyl group, of (XI) with HCl yields the monosubstituted piperazine (XII), which is finally condensed with (2R,3S)-oxirane (XIII) by means of LiClO4 in refluxing acetonitrile.
| 【1】 Abel, M.D.; Bathini, Y.; Ha, C.; et al.; Syn-2869, novel broad-spectrum antifungal triazole: Synthesis and structure activity relationships. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-148. |
| 【2】 Fromtling, R.A.; Castañer, J.; Syn-2869. Drugs Fut 1999, 24, 1, 30. |
| 【3】 Ha, C.; Unemi, N.; Nguyen, D.; Furukawa, T.; Sidhu, I.; Daneshtalab, M.; Bathini, Y.; Micetich, R.; Khan, J.; Abel, M.; Salama, S. (Synphar Laboratories Inc.; Taisho Pharmaceutical Co., Ltd.); New triazoles as therapeutic agents for fungal infections. EP 0889881; JP 2000507275; WO 9831675 . |
| 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) | 20299 | 1-(4-nitrophenyl)piperazine | 6269-89-2 | C10H13N3O2 | 详情 | 详情 |
| (II) | 13214 | Di-tert-butyldicarbonate; Dicarbonic acid bis(1,1-dimethylethyl) ester; dicarbonic acid di-tert-butyl ester pyrocarbonic acid di-tert-butyl ester; bis(1,1-dimethylethyl) dicarbonate di-tert-butyl pyrocarbonate | 24424-99-5 | C10H18O5 | 详情 | 详情 |
| (III) | 20301 | tert-butyl 4-(4-nitrophenyl)-1-piperazinecarboxylate | C15H21N3O4 | 详情 | 详情 | |
| (IV) | 20302 | tert-butyl 4-(4-aminophenyl)-1-piperazinecarboxylate | C15H23N3O2 | 详情 | 详情 | |
| (V) | 13580 | 1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate | 1885-14-9 | C7H5ClO2 | 详情 | 详情 |
| (VI) | 20304 | tert-butyl 4-[4-[(phenoxycarbonyl)amino]phenyl]-1-piperazinecarboxylate | C22H27N3O4 | 详情 | 详情 | |
| (VII) | 20305 | tert-butyl 4-[4-[(hydrazinocarbonyl)amino]phenyl]-1-piperazinecarboxylate | C16H25N5O3 | 详情 | 详情 | |
| (VIII) | 15369 | Iminoformamide; Methanimidamide | 463-52-5 | CH4N2 | 详情 | 详情 |
| (IX) | 20307 | tert-butyl 4-[4-(5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)phenyl]-1-piperazinecarboxylate | C17H23N5O3 | 详情 | 详情 | |
| (X) | 20308 | 4-(bromomethyl)phenyl trifluoromethyl ether; 1-(bromomethyl)-4-(trifluoromethoxy)benzene | 50824-05-0 | C8H6BrF3O | 详情 | 详情 |
| (XI) | 20309 | tert-butyl 4-(4-[5-oxo-1-[4-(trifluoromethoxy)benzyl]-1,5-dihydro-4H-1,2,4-triazol-4-yl]phenyl)-1-piperazinecarboxylate | C25H28F3N5O4 | 详情 | 详情 | |
| (XII) | 20310 | 4-[4-(1-piperazinyl)phenyl]-2-[4-(trifluoromethoxy)benzyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C20H20F3N5O2 | 详情 | 详情 | |
| (XIII) | 13114 | 1-[[(2S,3S)-2-(2,4-Difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole | C12H11F2N3O | 详情 | 详情 |