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【结 构 式】 
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【分子编号】30802 【品名】(2S)-2-[cyclohexyl(methyl)amino]-4-methylpentanoic acid 【CA登记号】 |
【 分 子 式 】C13H25NO2 【 分 子 量 】227.34704 【元素组成】C 68.68% H 11.08% N 6.16% O 14.07% |
合成路线1
该中间体在本合成路线中的序号：(VII)The precursor amino acid derivatives were obtained as follows: The condensation of N-Boc-O-benzyltyrosine (I) with tert-butylamine using O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) gave amide (II). Subsequent deprotection of the Boc group of (II) by means of trifluoroacetic acid provided O-benzyltyrosine tert-butyl amide (III). N-Methyl leucine benzyl ester (IV) was alkylated with 3-bromocyclohexene (V), yielding the cyclohexenyl amine (VI). Hydrogenation of the olefinic double bond of (VI) with concomitant benzyl ester hydrogenolysis in the presence of Pd/C furnished N-cyclohexyl-N-methylleucine (VII). The title dipeptide was finally obtained by HBTU-promoted coupling of amino acids (III) and (VII).
| 【1】 Ryder, T.R.; Hu, L.-Y.; Rafferty, M.F.; et al.; N,N-dialkyl-dipeptidylamines as novel N-type calcium channel blockers. Bioorg Med Chem Lett 1999, 9, 6, 907. |
| 【2】 Szoke, B.G.; Rafferty, M.F.; Silva, D.F.; Song, Y.; Malone, T.C.; Hu, L.-Y.; Urge, L.; Nadasdi, L.; Ryder, T.R. (Neurex Corp.; Pfizer Inc.); Substd. peptidylamine calcium channel blockers. WO 9854123 . |
| 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) | 30396 | (2S)-3-[4-(benzyloxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propionic acid | 54784-43-9 | C21H25NO5 | 详情 | 详情 |
| (II) | 30797 | tert-butyl (1S)-1-[4-(benzyloxy)benzyl]-2-(tert-butylamino)-2-oxoethylcarbamate | C25H34N2O4 | 详情 | 详情 | |
| (III) | 30798 | (2S)-2-amino-3-[4-(benzyloxy)phenyl]-N-(tert-butyl)propanamide | C20H26N2O2 | 详情 | 详情 | |
| (IV) | 30799 | benzyl (2S)-4-methyl-2-(methylamino)pentanoate | C14H21NO2 | 详情 | 详情 | |
| (V) | 30800 | 3-bromo-1-cyclohexene | 1521-51-3 | C6H9Br | 详情 | 详情 |
| (VI) | 30801 | benzyl (2S)-2-[2-cyclohexen-1-yl(methyl)amino]-4-methylpentanoate | C20H29NO2 | 详情 | 详情 | |
| (VII) | 30802 | (2S)-2-[cyclohexyl(methyl)amino]-4-methylpentanoic acid | C13H25NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Alternatively, the compound was prepared using polymer-supported resins. Dialkyl leucine (VII) was first treated with isobutyl chloroformate and morpholine resin, tyrosine derivative (III) was added, and was then treated with isocyanate resin and tris(2-aminomethyl)amine resin. Filtration of the insoluble resins provided a solution of pure dipeptide derivative.
| 【1】 Szoke, B.G.; Rafferty, M.F.; Silva, D.F.; Song, Y.; Malone, T.C.; Hu, L.-Y.; Urge, L.; Nadasdi, L.; Ryder, T.R. (Neurex Corp.; Pfizer Inc.); Substd. peptidylamine calcium channel blockers. WO 9854123 . |