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【结 构 式】 
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【药物名称】BMS-292655 【化学名称】3-(Phosphonooxymethyl)benzoic acid [2(R)-[4-(4-cyanophenyl)thiazol-2-yl]-1(R)-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-ylmethyl)propoxy]methyl ester sodium salt 【CA登记号】271250-73-8, 271250-72-7 (free acid) 【 分 子 式 】C31H25F2N5NaO7PS 【 分 子 量 】703.5986 |
【开发单位】Bristol-Myers Squibb (Originator) 【药理作用】Antifungal Agents, ANTIINFECTIVE THERAPY, Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems |
合成路线1
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 |
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| (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 |