【结 构 式】 |
【药物名称】 【化学名称】N-[1(S)-Formyl-3-methylbutyl]-4-methyl-2(R)-[2-(naphthalen-2-ylsulfonyl)ethyl]pentanamide 【CA登记号】 【 分 子 式 】C24H33NO4S 【 分 子 量 】431.59891 |
【开发单位】Cephalon (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of |
合成路线1
2-Naphtalenethiol (I) was treated with ethyl 4-bromobutyrate (II) and NaH to give thioether (III). Alkylation of (III) with isobutyl iodide (IV) in the presence of LDA afforded racemic (V), which was then hydrolyzed to the acid (VI) on treatment with litium hydroxide. Coupling of racemic acid (VI) with (S)-leucinol (VII) yielded a mixture of diastereomeric amides, which were separated by column chromatography. Diastereoisomer (VIII) was oxidized with m-chloroperbenzoic acid to give sulfone (IX), and was further oxidized with DMSO and sulfur trioxide-pyridine complex to produce the target aldehyde.
【1】 Chatterjee, S.; et al.; Nonpeptidic inhibitors of recombinant human calpain; I. Bioorg Med Chem Lett 1997, 7, 3, 287-290. |
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) | 15234 | 2-Naphthalenethiol; 2-Naphthylhydrosulfide | 91-60-1 | C10H8S | 详情 | 详情 |
(II) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
(III) | 18167 | ethyl 4-(2-naphthylsulfanyl)butanoate | C16H18O2S | 详情 | 详情 | |
(IV) | 18168 | 1-iodo-2-methylpropane | 513-38-2 | C4H9I | 详情 | 详情 |
(V) | 18169 | ethyl 4-methyl-2-[2-(2-naphthylsulfanyl)ethyl]pentanoate | C20H26O2S | 详情 | 详情 | |
(VI) | 18170 | 4-methyl-2-[2-(2-naphthylsulfanyl)ethyl]pentanoic acid | C18H22O2S | 详情 | 详情 | |
(VII) | 18171 | L-(+)-leucinol; (S)-2-amino-4-methyl-1-pentanol; (2S)-2-amino-4-methyl-1-pentanol | 7533-40-6 | C6H15NO | 详情 | 详情 |
(VIII) | 18172 | (2R)-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-4-methyl-2-[2-(2-naphthylsulfanyl)ethyl]pentanamide | C24H35NO2S | 详情 | 详情 | |
(IX) | 18173 | (2R)-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-4-methyl-2-[2-(2-naphthylsulfonyl)ethyl]pentanamide | C24H35NO4S | 详情 | 详情 |