【结 构 式】 |
【分子编号】37267 【品名】methyl (2S)-2-[[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino]-3-methylbutanoate 【CA登记号】 |
【 分 子 式 】C20H22N2O2 【 分 子 量 】322.40696 【元素组成】C 74.51% H 6.88% N 8.69% O 9.92% |
合成路线1
该中间体在本合成路线中的序号:(V)This compound has been obtained by two related ways: 1) The hydrolysis of 4'-(bromomethyl)biphenyl-2-carbonitrile (I) with NaOAc in refluxing acetic acid gives the corresponding carbinol (II), which is oxidized with oxalyl chloride in DMSO/dichloromethane yielding the aldehyde (III). The reductocondensation of (III) with L-valine methyl ester (IV) by means of NaBH4CN in THF affords the N-alkylated valine (V), which is acylated with pentanoyl chloride (VI) and TEA in dichloromethane providing the pentanamide (VII). The reaction of the CN group of (VII) with tributyltin azide in refluxing xylene gives the tetrazol derivative (VIII). Finally, the ester group of (VIII) is hydrolyzed with NaOH to furnish the target compound. 2) L-valine methyl ester (IV) can be condensed directly with the bromo-methyl derivative (I) by means of DIEA in dichloromethane giving the N-alkylated valine (V) already reported.
【1】 Buhlmayer, P.; Ostermayer, F.; Schmidlin, T. (Novartis AG); Acyl cpds.. EP 0443983; JP 1992235149; US 5399578; US 5965592 . |
【2】 Buhlmayer, P.; et al.; Valsartan, a potent, orally active angiotensin II antagonist developed from the structurally new amino acid series. Bioorg Med Chem Lett 1994, 4, 1, 29. |
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) | 15332 | 4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile; 4'-bromomethyl-2-cyanobiphenyl | 114772-54-2 | C14H10BrN | 详情 | 详情 |
(II) | 37265 | 4'-(hydroxymethyl)[1,1'-biphenyl]-2-carbonitrile | C14H11NO | 详情 | 详情 | |
(III) | 37266 | 4'-formyl[1,1'-biphenyl]-2-carbonitrile | C14H9NO | 详情 | 详情 | |
(IV) | 16613 | methyl (2S)-2-amino-3-methylbutanoate | C6H13NO2 | 详情 | 详情 | |
(V) | 37267 | methyl (2S)-2-[[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino]-3-methylbutanoate | C20H22N2O2 | 详情 | 详情 | |
(VI) | 15116 | pentanoyl chloride; valeryl chloride | 638-29-9 | C5H9ClO | 详情 | 详情 |
(VII) | 37268 | methyl (2S)-2-[[(2'-cyano[1,1'-biphenyl]-4-yl)methyl](pentanoyl)amino]-3-methylbutanoate | C25H30N2O3 | 详情 | 详情 | |
(VIII) | 37269 | methyl (2S)-3-methyl-2-(pentanoyl[[2'-(1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]amino)butanoate | C25H31N5O3 | 详情 | 详情 |