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【结 构 式】 
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【分子编号】45264 【品名】4'-methyl[1,1'-biphenyl]-2-carbonitrile 【CA登记号】 |
【 分 子 式 】C14H11N 【 分 子 量 】193.24808 【元素组成】C 87.01% H 5.74% N 7.25% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of 2-bromo-4'-methylbiphenyl (I) with 14C labeled cuprous cyanide in refluxing DMF gives 4'-methylbiphenyl-2-carbonitrile (II), which is brominated with NBS and AIBN in refluxing CCl4 to yield the bromomethyl derivative (III). The condensation of (III) with L-valine benzyl ester (IV) by means of DIEA in hot DMF affords the N-substituted valine (V), which is acylated with pentanoyl chloride (VI) and DIEA to provide the N-acylated valine (VII). The cyclization of the cyano group of (VII) with tributyltin azide at 140 C furnishes the tetrazol derivative (VIII) which is finally debenzylated by hydrogenation with H2 over Pd/C in dioxane.
| 【1】 Moenius, T.; et al.; Carbon-14 labelling of Diovan(TM) in its valine-moiety. J Label Compd Radiopharm 2000, 43, 13, 1245. |
| 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) | 41935 | 2-bromo-4'-methyl-1,1'-biphenyl | C13H11Br | 详情 | 详情 | |
| (II) | 13929 | 2-Cyano-4'-methylbiphenyl; 4'-Methyl[1,1'-biphenyl]-2-carbonitrile | 114772-53-1 | C14H11N | 详情 | 详情 |
| (II) | 45264 | 4'-methyl[1,1'-biphenyl]-2-carbonitrile | C14H11N | 详情 | 详情 | |
| (III) | 15332 | 4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile; 4'-bromomethyl-2-cyanobiphenyl | 114772-54-2 | C14H10BrN | 详情 | 详情 |
| (III) | 45265 | 4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile | C14H10BrN | 详情 | 详情 | |
| (IV) | 41936 | benzyl (2S)-2-amino-3-methylbutanoate | C12H17NO2 | 详情 | 详情 | |
| (V) | 41937 | benzyl (2S)-2-[[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino]-3-methylbutanoate; N-[(2'-cyanobiphenyl-4-yl)methyl]-L-valine benzyl ester | 137864-23-4 | C26H26N2O2 | 详情 | 详情 |
| (V) | 45266 | benzyl (2S)-2-[[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino]-3-methylbutanoate | C26H26N2O2 | 详情 | 详情 | |
| (VI) | 15116 | pentanoyl chloride; valeryl chloride | 638-29-9 | C5H9ClO | 详情 | 详情 |
| (VII) | 41938 | benzyl (2S)-2-[[(2'-cyano[1,1'-biphenyl]-4-yl)methyl](pentanoyl)amino]-3-methylbutanoate | C31H34N2O3 | 详情 | 详情 | |
| (VII) | 45267 | benzyl (2S)-2-[[(2'-cyano[1,1'-biphenyl]-4-yl)methyl](pentanoyl)amino]-3-methylbutanoate | C31H34N2O3 | 详情 | 详情 | |
| (VIII) | 41939 | benzyl (2S)-3-methyl-2-(pentanoyl[[2'-(1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]amino)butanoate | C31H35N5O3 | 详情 | 详情 | |
| (VIII) | 45268 | benzyl (2S)-3-methyl-2-(pentanoyl[[2'-(1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]amino)butanoate | C31H35N5O3 | 详情 | 详情 |