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【结 构 式】 
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【药物名称】DIBA-4, NSC-672594, CI-1013, PD-159206 【化学名称】N,N'-Dithiobis(2,1-phenylene)bis(carbonyl)bis(L-isoleucine) 【CA登记号】171744-42-6 【 分 子 式 】C26H32N2O6S2 【 分 子 量 】532.68274 |
【开发单位】Pfizer (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Antiviral Drugs |
合成路线1
The protection of aniline (I) with di-tert-butyl dicarbonate in THF gives the carbamate (II), which is treated with BuLi and 14C labeled CO2 in THF yielding 2-(tert-butoxycarbonylamino)benzoic acid (III). The deprotection of (III) with TFA in dichloromethane affords labeled 2-aminobenzoic acid (IV), which is diazotized with NaNO2 /HCl and treated with Na2S, S and NaOH to give the disulfide (V). The reaction of (V) with refluxing SOCl2 yields the acid dichloride (VI), which is condensed with L-isoleucine tert-butyl ester (VII), by means of N-methylmorpholine (NMM) in dichloromethane to afford the final intermediate (VIII). Finally, this compound is deprotected with TFA in dichloromethane to give the labeled target compound.
| 【1】 Fiore, P.J.; et al.; Development and pilot-scale demonstration of a process for inhibitors of the HIV nucleocapsid protein, NCp7. Org Process Res Dev 1998, 2, 3, 151. |
| 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) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (II) | 32735 | tert-butyl phenylcarbamate | 3422-01-3 | C11H15NO2 | 详情 | 详情 |
| (III) | 32736 | 2-[(tert-butoxycarbonyl)amino]benzoic acid | 68790-38-5 | C12H15NO4 | 详情 | 详情 |
| (III) | 45324 | 2-[(tert-butoxycarbonyl)amino]benzoic acid | C12H15NO4 | 详情 | 详情 | |
| (IV) | 11661 | 2-Aminobenzoic acid;Anthranilic acid; o-Aminobenzoic acid | 118-92-3 | C7H7NO2 | 详情 | 详情 |
| (IV) | 45325 | 2-aminobenzoic acid | C7H7NO2 | 详情 | 详情 | |
| (V) | 20404 | 2-[(2-carboxyphenyl)disulfanyl]benzoic acid; 2,2'-Dithiodibenzoic acid | 119-80-2 | C14H10O4S2 | 详情 | 详情 |
| (V) | 45326 | 2-[(2-carboxyphenyl)disulfanyl]benzoic acid | C14H10O4S2 | 详情 | 详情 | |
| (VI) | 20405 | 2-[[2-(chlorocarbonyl)phenyl]disulfanyl]benzoyl chloride | C14H8Cl2O2S2 | 详情 | 详情 | |
| (VI) | 45327 | 2-[[2-(chlorocarbonyl)phenyl]disulfanyl]benzoyl chloride | C14H8Cl2O2S2 | 详情 | 详情 | |
| (VII) | 32737 | tert-butyl (2S,3S)-2-amino-3-methylpentanoate | C10H21NO2 | 详情 | 详情 | |
| (VIII) | 32738 | tert-butyl (2S,3S)-2-[(2-[[2-([[(1S,2S)-1-(tert-butoxycarbonyl)-2-methylbutyl]amino]carbonyl)phenyl]disulfanyl]benzoyl)amino]-3-methylpentanoate | C34H48N2O6S2 | 详情 | 详情 | |
| (VIII) | 45328 | tert-butyl (2S,3S)-2-[(2-[[2-([[(1S,2S)-1-(tert-butoxycarbonyl)-2-methylbutyl]amino]carbonyl)phenyl]disulfanyl]benzoyl)amino]-3-methylpentanoate | C34H48N2O6S2 | 详情 | 详情 |
合成路线2
The reaction of disulfide (I) with SOCl2 gives the corresponding acyl chloride (II), which is then condensed with L-isoleucine (III) by means of NaHCO3 in THF.
| 【1】 Fiore, P.J.; et al.; Development and pilot-scale demonstration of a process for inhibitors of the HIV nucleocapsid protein, NCp7. Org Process Res Dev 1998, 2, 3, 151. |