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【结 构 式】 
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【药物名称】D-43787 【化学名称】Nepsilon-(Benzyloxycarbonyl)-Nalpha-[1-[1-(tert-butoxycarbonyl)indolin-2(S)-ylcarbonyl]indolin-2(S)-ylcarbonyl]-L-lysine methyl ester 【CA登记号】198016-44-3 (diastereomer) 【 分 子 式 】C38H44N4O8 【 分 子 量 】684.79638 |
【开发单位】Asta Medica (Originator), Ivax (Codevelopment) 【药理作用】Antiallergy/Antiasthmatic Drugs, Antiarthritic Drugs, Asthma Therapy, IMMUNOMODULATING AGENTS, Immunosuppressants, RESPIRATORY DRUGS, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Peptidylprolyl Isomerase Inhibitors |
合成路线1
Indoline-2-carboxylic acid (I) is converted into the N-Boc derivative (II) by treatment with Boc2O. Subsequent coupling of (II) with methyl indoline-2-carboxylate (III) by using 2-chloro-1-methylpyridinium iodide (CMPI) provides amide (IV). Hydrolysis of the methyl ester function of (IV) employing LiOH leads to carboxylic acid (V). This is then coupled to N-epsilon-(benzyloxycarbonyl)-lysine methyl ester (VI) in the presence of CMPI to furnish the title compound.
| 【1】 Reichert, D.; Kutscher, B.; Bang, H.; Brune, K.; Quinkert, G.; Schaible, H.-G. (Asta Medica AG); Specific immunophilin ligands as antiasthmatics and immunosuppressants. DE 19616509; EP 0896580; JP 2000500776; WO 9741148 . |
| 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) | 34308 | ethyl (2S)-2,3-dihydro-1H-indole-2-carboxylate | C11H13NO2 | 详情 | 详情 | |
| (II) | 61011 | 1-(tert-butoxycarbonyl)-2-indolinecarboxylic acid | C14H17NO4 | 详情 | 详情 | |
| (III) | 61012 | methyl 2-indolinecarboxylate | C10H11NO2 | 详情 | 详情 | |
| (IV) | 61013 | tert-butyl 2-{[2-(methoxycarbonyl)-2,3-dihydro-1H-indol-1-yl]carbonyl}-1-indolinecarboxylate | C24H26N2O5 | 详情 | 详情 | |
| (V) | 61014 | 1-{[1-(tert-butoxycarbonyl)-2,3-dihydro-1H-indol-2-yl]carbonyl}-2-indolinecarboxylic acid | C23H24N2O5 | 详情 | 详情 | |
| (VI) | 31069 | methyl (2S)-2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate | C15H22N2O4 | 详情 | 详情 |