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【结 构 式】 
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【分子编号】60212 【品名】4-{2-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-1,3-thiazol-4-yl}benzonitrile 【CA登记号】 |
【 分 子 式 】C22H17F2N5OS 【 分 子 量 】437.4728864 【元素组成】C 60.4% H 3.92% F 8.69% N 16.01% O 3.66% S 7.33% |
合成路线1
该中间体在本合成路线中的序号：(I)The condensation of BMS-207147 (I) with phosphoric acid di-tert-butyl chloromethyl triester (II) by means of NaH in THF gives the phosphoric triester (III), which is finally hydrolyzed with TFA in dichloromethane and treated with Na2CO3 to provide the target disodium salt.
| 【1】 Ueda, Y.; Barbour, N.; Bronson, J.J.; et al.; BMS-379224, a water-soluble prodrug of ravuconazole. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-817. |
| 【2】 Hudyma, T.W.; Golik, J.; Ueda, Y.; Chen, C.-P.; Matiskella, J.D. (Bristol-Myers Squibb Co.); Water soluble prodrugs of azole cpds.. EP 1284737; US 6362172; WO 0152852 . |
| 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) | 60212 | 4-{2-[2-(2,4-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 | |
| (II) | 42239 | di(tert-butyl) chloromethyl phosphate;di-tert-butyl chloromethyl phosphate；PHOSPHORIC ACI DI-T-BUTYL EXTER CHLOROMETHYL ESTER | 229625-50-7 | C9H20ClO4P | 详情 | 详情 |
| (III) | 60217 | {[2-[4-(4-cyanophenyl)-1,3-thiazol-2-yl]-1-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-ylmethyl)propyl]oxy}methyl bis(1,1-dimethylethyl) phosphate | C31H36F2N5O5PS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The condensation of BMS-207147 (I) with 3-(chloromethyl)benzoic acid chloromethyl ester (II) (obtained by esterification of 3-(chloromethyl)benzoyl chloride (III) with paraformaldehyde and ZnCl2) by means of KH in THF gives the adduct (IV), which is condensed with phosphoric acid di-tert-butyl ester (V) to yield the phosphate (V). Finally, this compound is hydrolyzed with TFA in dichloromethane and treated with NaHCO3 to provide the target sodium salt.
| 【1】 Hudyma, T.W.; Zheng, X.; Clark, J.; et al.; BMS-292655, a soluble prodrug of the clinically efficacious antifungal triazole, BMS-207147 (ravuconazole). 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-816. |
| 【2】 Hudyma, T.W.; Kim, O.K.; Zheng, X. (Bristol-Myers Squibb Co.); Water soluble prodrugs of azole cpds.. WO 0030655 . |
| 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) | 60212 | 4-{2-[2-(2,4-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 | |
| (II) | 60213 | chloromethyl 3-(chloromethyl)benzoate | C9H8Cl2O2 | 详情 | 详情 | |
| (III) | 25107 | 3-(chloromethyl)benzoyl chloride | 63024-77-1 | C8H6Cl2O | 详情 | 详情 |
| (IV) | 20214 | ethyl (3S)-3-benzyl-2-oxo-3-piperidinecarboxylate | C15H19NO3 | 详情 | 详情 | |
| (V) | 60215 | bis(1,1-dimethylethyl) hydrogen phosphate | C8H19O4P | 详情 | 详情 | |
| (VI) | 60216 | {[2-[4-(4-cyanophenyl)-1,3-thiazol-2-yl]-1-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-ylmethyl)propyl]oxy}methyl 3-[({bis[(1,1-dimethylethyl)oxy]phosphoryl}oxy)methyl]benzoate | C39H42F2N5O7PS | 详情 | 详情 |