3-(5-chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one -Drug Synthesis Database

【结构式】

【分子编号】43889

【品名】3-(5-chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one

【CA登记号】

【分子式】C₁₆H₁₀ClF₄NO₂

【分子量】359.7072528

【元素组成】C 53.43% H 2.8% Cl 9.86% F 21.13% N 3.89% O 8.9%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VIII)

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.

参考文献中间体

合成目标

【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：(III)

The methylation of the phenolic OH of indanone (I) with tritium labeled methyl iodide and Cs2CO3 gives the methyl ether (II). The fluorination of the remaining OH of (II) with DAST yields the target compound as a racemic mixture, that is optically resolved by chiral HPLC.

参考文献中间体

合成目标

【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	分子式	供应商	用于合成
(I)	64259	3-(5-chloro-2-hydroxyphenyl)-3-hydroxy-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one	C₁₅H₉ClF₃NO₃	详情	详情
(II)	39339	3-(5-chloro-2-methoxyphenyl)-3-hydroxy-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one	C₁₆H₁₁ClF₃NO₃	详情	详情
(II)	64260	3-(5-chloro-2-methoxyphenyl)-3-hydroxy-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one	C₁₆H₁₁ClF₃NO₃	详情	详情
(III)	43889	3-(5-chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one	C₁₆H₁₀ClF₄NO₂	详情	详情
(III)	64261	3-(5-chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one	C₁₆H₁₀ClF₄NO₂	详情	详情

Extended Information