|
【结 构 式】 
|
【分子编号】45328 【品名】tert-butyl (2S,3S)-2-[(2-[[2-([[(1S,2S)-1-(tert-butoxycarbonyl)-2-methylbutyl]amino]carbonyl)phenyl]disulfanyl]benzoyl)amino]-3-methylpentanoate 【CA登记号】 |
【 分 子 式 】C34H48N2O6S2 【 分 子 量 】644.897 【元素组成】C 63.32% H 7.5% N 4.34% O 14.89% S 9.94% |
合成路线1
该中间体在本合成路线中的序号：(VIII)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
该中间体在本合成路线中的序号：(VIII)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 intermediate (VIII). The deprotectionof (VIII) with TFA in dichloromethane to give the labeled dimeric isoleucine derivative (IX), which is finally cyclized to the target benazoisothiazolone by oxidative cyclization with Br2 in dichloromethane.
| 【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 | |
| (IX) | 32740 | (2S,3S)-2-[(2-[[2-([[(1S,2S)-1-carboxy-2-methylbutyl]amino]carbonyl)phenyl]disulfanyl]benzoyl)amino]-3-methylpentanoic acid | C26H32N2O6S2 | 详情 | 详情 | |
| (IX) | 45329 | (2S,3S)-2-[(2-[[2-([[(1S,2S)-1-carboxy-2-methylbutyl]amino]carbonyl)phenyl]disulfanyl]benzoyl)amino]-3-methylpentanoic acid | C26H32N2O6S2 | 详情 | 详情 |