2,4-二氯-5-三氟甲基嘧啶合成路线 （共 12 条）
反应条件
phosphoric acid; N-ethyl-N,N-diisopropylamine; trichlorophosphate T=85 - 100°C; 20 h;
参考文献
US2005/256145 A1, ;
Page/Page column 43 ;
反应条件
acetic acid; zinc in tetrahydrofuran
参考文献
ASTEX THERAPEUTICS LIMITED; ASTEX THERAPEUTICS LIMITED
Patent: WO2009/150240 A1, 2009 ;
Location in patent: Page/Page column 132 ;
WO 2009/150240 A1
反应条件
1: N-ethyl-N,N-diisopropylamine / butan-1-ol / 5 h / 0 - 20 °C 2: trifluoroacetic acid / dichloromethane / 0 - 20 °C 3: N-ethyl-N,N-diisopropylamine / dichloromethane / -30 - 20 °C 4: 1,4-dioxane / 50 °C 5: sodium carbonate / dichloromethane / 0.58 h / 0 - 20 °C View Scheme
参考文献
CELGENE AVILOMICS RESEARCH, INC.; LAI, Mei; WITOWSKI, Steven, Richard; TESTER, Richland, Wayne; LEE, Kwangho
Patent: WO2013/138502 A1, 2013 ;
反应条件
triethylamine in anhydrous dichloroethane; tert-butyl alcohol
参考文献
PFIZER PRODUCTS INC.
Patent: WO2005/23780 A1, 2005 ;
Location in patent: Page/Page column 9-10 ;
反应条件
in tetrahydrofuran
T=-25 - 20°C; 1 h;
参考文献
Zahn, Stephan Karl; Boehmelt, Guido; Mantoulidis, Andreas; Reiser, Ulrich; Treu, Matthias; Guertler, Ulrich; Schoop, Andreas; Solca, Flavio; Tontsch-Grunt, Ulrike; Brueckner, Ralph; Reither, Charlotte; Herfurth, Lars; Kraemer, Oliver; Stadtmueller, Heinz; Engelhardt, Harald
Patent: US2007/32514 A1, 2007 ;
Location in patent: Page/Page column 10-11 ;
US 20070032514 A1
反应条件
1: 2,4-dichloro-5-trifluoromethyl-pyrimidine With zinc(II) chloride in tetrahydrofuran; diethyl ether
2 h; Cooling with iceInert atmosphere;
2: sodium thiomethoxide in tetrahydrofuran; diethyl ether
T=20°C;
参考文献
CANCER THERAPEUTICS CRC PTY LTD; DEVLIN, Mark Graeme; STREET, Ian Philip; TONG, Warwick Bonner
Patent: WO2014/27199 A1, 2014 ;
Location in patent: Page/Page column 61 ;
反应条件
in tetrahydrofuran
T=-25 - 20°C; 1 h;
参考文献
Zahn, Stephan Karl; Boehmelt, Guido; Mantoulidis, Andreas; Reiser, Ulrich; Treu, Matthias; Guertler, Ulrich; Schoop, Andreas; Solca, Flavio; Tontsch-Grunt, Ulrike; Brueckner, Ralph; Reither, Charlotte; Herfurth, Lars; Kraemer, Oliver; Stadtmueller, Heinz; Engelhardt, Harald
Patent: US2007/32514 A1, 2007 ;
Location in patent: Page/Page column 10-11 ;
US 20070032514 A1
反应条件
1.1: zinc dibromide / 1,2-dichloro-ethane; tert-butyl alcohol / 0.5 h
1.2: 35 °C / Industry scale
2.1: diisopropylamine / isopropyl alcohol; toluene / 6.4 h / 10 - 90 °C / Industry scale
3.1: ethanol; water / 70 °C / Industry scale
View Scheme
参考文献
Pfizer Inc.
Patent: US2011/33441 A1, 2011 ;
反应条件
1.1: zinc dibromide / 1,2-dichloro-ethane; tert-butyl alcohol / 0.5 h
1.2: 35 °C / Industry scale
2.1: diisopropylamine / isopropyl alcohol; toluene / 6.4 h / 10 - 90 °C / Industry scale
3.1: tetrahydrofuran / 24 h / 20 °C
View Scheme
参考文献
Pfizer Inc.
Patent: US2011/33441 A1, 2011 ;
反应条件
1: 2,4-dichloro-5-trifluoromethyl-pyrimidine With zinc(II) chloride in diethyl ether; 1,2-dichloro-ethane; tert-butyl alcohol
T=0°C;
2: 4-methoxy-aniline With triethylamine in diethyl ether; 1,2-dichloro-ethane; tert-butyl alcohol
T=20°C;
参考文献
Richter, Daniel T.; Kath, John C.; Luzzio, Michael J.; Keene, Nandell; Berliner, Martin A.; Wessel, Matthew D.
Tetrahedron Letters, 2013 , vol. 54, # 35 p. 4610 - 4612
