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【结 构 式】 
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【分子编号】64193 【品名】allyl (2R,3S,4R,5R)-2-[({(2R,3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-[(Z)-11-octadecenoylamino]tetrahydro-2H-pyran-2-yl}oxy)methyl]-6-{[tert-butyl(dimethyl)silyl]oxy}-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-3-yl carbonate 【CA登记号】 |
【 分 子 式 】C82H151N2O18PSi 【 分 子 量 】1512.162882 【元素组成】C 65.13% H 10.06% N 1.85% O 19.04% P 2.05% Si 1.86% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of 3-(trifluoromethyl)aniline (I) with Boc2O gives the carbamate (II), which is condensed with 14C labeled diethyl oxalate (III) by means of BuLi to yield the ketoester (IV). The cyclization of (IV) by means of refluxing aq. HCl affords the labeled 6-(trifluoromethyl)isatin (V), which is condensed with 5-chloro-2-methoxyphenylmagnesium bromide (VI) to provide the hydroxyketone (VII). The fluorination of (VII) with DAST gives the target compound as a racemic mixture (VIII), which is finally submitted to optical resolution by chiral HPLC.
| 【1】 Dischino, D.D.; Gribkoff, V.K.; Hewawasam, P.; Luke, G.M.; Rinehart, J.K.; Spears, T.L.; Starrett, J.E. Jr.; Synthesis of 3H and 14C labeled (S)-3-(5-chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indol-2-one, MaxiPost(TM). An agent for post-stroke neuroprotection. J Label Compd Radiopharm 2003, 46, 2, 139. |
| 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) | 26347 | 3-(trifluoromethyl)phenylamine; 3-(trifluoromethyl)aniline; 3-aminobenzotrifluoride | 98-16-8 | C7H6F3N | 详情 | 详情 |
| (II) | 39335 | tert-butyl 3-(trifluoromethyl)phenylcarbamate | C12H14F3NO2 | 详情 | 详情 | |
| (III) | 17571 | Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate | 95-92-1 | C6H10O4 | 详情 | 详情 |
| (III) | 64193 | allyl (2R,3S,4R,5R)-2-[({(2R,3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-[(Z)-11-octadecenoylamino]tetrahydro-2H-pyran-2-yl}oxy)methyl]-6-{[tert-butyl(dimethyl)silyl]oxy}-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-3-yl carbonate | C82H151N2O18PSi | 详情 | 详情 | |
| (IV) | 39336 | ethyl 2-[2-[(tert-butoxycarbonyl)amino]-4-(trifluoromethyl)phenyl]-2-oxoacetate | C16H18F3NO5 | 详情 | 详情 | |
| (IV) | 64197 | ethyl 2-[2-[(tert-butoxycarbonyl)amino]-4-(trifluoromethyl)phenyl]-2-oxoacetate | C16H18F3NO5 | 详情 | 详情 | |
| (V) | 39337 | 6-(trifluoromethyl)-1H-indole-2,3-dione | C9H4F3NO2 | 详情 | 详情 | |
| (V) | 64198 | 6-(trifluoromethyl)-1H-indole-2,3-dione | C9H4F3NO2 | 详情 | 详情 | |
| (VI) | 39338 | bromo(5-chloro-2-methoxyphenyl)magnesium | C7H6BrClMgO | 详情 | 详情 | |
| (VII) | 39339 | 3-(5-chloro-2-methoxyphenyl)-3-hydroxy-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one | C16H11ClF3NO3 | 详情 | 详情 | |
| (VII) | 64199 | 3-(5-chloro-2-methoxyphenyl)-3-hydroxy-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one | C16H11ClF3NO3 | 详情 | 详情 | |
| (VIII) | 43889 | 3-(5-chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one | C16H10ClF4NO2 | 详情 | 详情 | |
| (VIII) | 64200 | 3-(5-Chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-2,3-dihydro-1H-indol-2-one | C16H10ClF4NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LXIII)Amine (LX) was acylated with cis-vaccenic acid (LXI) to produce amide (LXII). This was desilylated by means of HF yielding alcohol (XXXIX), which was finally converted to the title compound using the same sequence as in Scheme 27814501f.
| 【1】 Kobayashi, S.; Kawata, T.; Christ, W.J.; Rossignol, D.P. (Eisai Co., Ltd.); Substd. liposaccharides useful in the treatment and prevention of endotoxemia. US 5750664; WO 9639411 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIX) | 64171 | allyl (2R,3S,4R,5R)-2-[({(2R,3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-[(Z)-11-octadecenoylamino]tetrahydro-2H-pyran-2-yl}oxy)methyl]-4-(decyloxy)-6-hydroxy-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-3-yl carbonate | C76H137N2O18P | 详情 | 详情 | |
| (LX) | 64191 | allyl (2R,3S,4R,5R)-2-({[(2R,3R,4R,5S,6R)-3-amino-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-2-yl]oxy}methyl)-6-{[tert-butyl(dimethyl)silyl]oxy}-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-3-yl carbonate | C64H119N2O17PSi | 详情 | 详情 | |
| (LXI) | 64192 | (Z)-11-octadecenoic acid | C18H34O2 | 详情 | 详情 | |
| (LXIII) | 64193 | allyl (2R,3S,4R,5R)-2-[({(2R,3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-[(Z)-11-octadecenoylamino]tetrahydro-2H-pyran-2-yl}oxy)methyl]-6-{[tert-butyl(dimethyl)silyl]oxy}-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-3-yl carbonate | C82H151N2O18PSi | 详情 | 详情 |