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【结 构 式】 
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【分子编号】13935 【品名】5-(3'-Bromo-4'-methyl[1,1'-biphenyl]-2-yl)-1-trityl-1H-1,2,3,4-tetraazole 【CA登记号】 |
【 分 子 式 】C33H25BrN4 【 分 子 量 】557.49246 【元素组成】C 71.1% H 4.52% Br 14.33% N 10.05% |
合成路线1
该中间体在本合成路线中的序号：(III)A synthesis of [14C]-losartan has been described: The bromination of 4'-methylbiphenyl-2-carbonitrile (I) with Br2 and silver trifluoroacetate in dichloromethane gives 3'-bromo-4'-methylbiphenyl-2-carbonitrile (II), which is treated first with trimethylstannyl azide in refluxing toluene, and then with trityl chloride and triethylamine in hot dichloromethane, yielding 5-(3'-bromo-4'-methylbiphenyl-2-yl)-2-(triphenylmethyl)tetrazole (III). The bromination of (III) with N-bromosuccinimide (NBS) in refluxing carbon tetrachloride affords the corresponding bromomethyl derivative (IV), which is then condensed with 2-butyl-5-(tert-butyldimethylsilyloxymethyl)-4-chloro-1H-imidazole (V) by means of NaH in DMF to give (VI). The deprotection of (VI) with HCl in methanol yields the bromolosartan derivative (VII), which is finally tritiated by debromination with tritiated sodium borohydride and palladium acetate in methanol-THF.
| 【1】 Rivero, R.A.; Chen, R.; Chakravarty, P.K.; Rosegay, A.; Greenlee, W.J.; Simpson, R.; The synthesis of [3H]-losartan, [3H]-L-158,641 and [3H]-L-158,809. Bioorg Med Chem Lett 1993, 3, 4, 557. |
| 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) | 13929 | 2-Cyano-4'-methylbiphenyl; 4'-Methyl[1,1'-biphenyl]-2-carbonitrile | 114772-53-1 | C14H11N | 详情 | 详情 |
| (II) | 13934 | 3'-Bromo-4'-methyl[1,1'-biphenyl]-2-carbonitrile | C14H10BrN | 详情 | 详情 | |
| (III) | 13935 | 5-(3'-Bromo-4'-methyl[1,1'-biphenyl]-2-yl)-1-trityl-1H-1,2,3,4-tetraazole | C33H25BrN4 | 详情 | 详情 | |
| (IV) | 13936 | 5-[3'-Bromo-4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1-trityl-1H-1,2,3,4-tetraazole | C33H24Br2N4 | 详情 | 详情 | |
| (V) | 13937 | (2-Butyl-4-chloro-1H-imidazol-5-yl)methyl tert-butyl(dimethyl)silyl ether; 2-Butyl-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-chloro-1H-imidazole | C14H27ClN2OSi | 详情 | 详情 | |
| (VI) | 13938 | (1-[[3-Bromo-2'-(1-trityl-1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-2-butyl-4-chloro-1H-imidazol-5-yl)methanol | C41H36BrClN6O | 详情 | 详情 | |
| (VII) | 13939 | (1-[[3-Bromo-2'-(1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-2-butyl-4-chloro-1H-imidazol-5-yl)methanol | C22H22BrClN6O | 详情 | 详情 |