5-氯-4-氟-1H-吲哚-2-羧酸甲酯合成路线 （共 10 条）
反应条件
1: 5-chloro-4-fluoro-1H-indole-2-carboxylic acid With 1,1'-carbonyldiimidazole in N,N-dimethyl-formamide
T=20°C; 3.33333 h;
2: methanol in N,N-dimethyl-formamide
T=24°C; 3 h;
参考文献
IDENIX PHARMACEUTICALS, INC.
Patent: WO2008/42240 A2, 2008 ;
Location in patent: Page/Page column 112; 116-117 ;
反应条件
in xylene
T=130 - 140°C; 3 h;
参考文献
DAIICHI PHARMACEUTICAL CO., LTD.
Patent: EP1577301 A1, 2005 ;
Location in patent: Page/Page column 207-208 ;
反应条件
sodium chloride in methanol; anhydrous xylene; water
参考文献
DAIICHI PHARMACEUTICAL CO., LTD.
Patent: US2005/20645 A1, 2005 ;
反应条件
1: 2-azido-3-[(3-chloro-2-fluoro)phenyl]acrylic acid methyl ester in xylene
T=130 - 140°C; 3 h;
2: methyl 2-azidoacetate; 2-fluoro-3-chloro-benzaldehyde T=-20 - 0°C; 2.83333 h;
3: 1-(bromomethyl)-3-chloro-2-fluorobenzene T=20°C; 3.5 h;
参考文献
DAIICHI PHARMACEUTICAL CO., LTD.
Patent: EP1405852 A1, 2004 ;
Location in patent: Page 188 ;
EP 1405852 A1
反应条件
1: 5-chloro-4-fluoro-1H-indole-2-carboxylic acid With 1,1'-carbonyldiimidazole in N,N-dimethyl-formamide
T=20 - 25°C; 3 h; Inert atmosphere;
2: methanol in N,N-dimethyl-formamide
T=20 - 25°C; 3 h; Inert atmosphere;
参考文献
Mayes, Benjamin A.; Chaudhuri, Narayan C.; Hencken, Christopher P.; Jeannot, Frederic; Latham, G. Mark; Mathieu, Steven; Mcgarry, F. Patrick; Stewart, Alistair J.; Wang, Jingyang; Moussa, Adel
Organic Process Research and Development, 2010 , vol. 14, # 5 p. 1248 - 1253
反应条件
1.1: n-butyllithium / tetrahydrofuran; hexane / 2.67 h / -80 - -75 °C / Inert atmosphere
1.2: 17 h / -80 - -30 °C / Inert atmosphere
2.1: hydrogenchloride; water / ethanol / 2 h / 5 - 55 °C / Inert atmosphere
2.2: 1 h / 5 - 15 °C / Inert atmosphere
3.1: 1,4-diaza-bicyclo[2.2.2]octane / N,N-dimethyl-formamide / 20 - 36 °C / Inert atmosphere
3.2: 18 h / 20 - 100 °C / Inert atmosphere
4.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 3 h / 20 - 25 °C / Inert atmosphere
4.2: 3 h / 20 - 25 °C / Inert atmosphere
View Scheme
参考文献
Mayes, Benjamin A.; Chaudhuri, Narayan C.; Hencken, Christopher P.; Jeannot, Frederic; Latham, G. Mark; Mathieu, Steven; Mcgarry, F. Patrick; Stewart, Alistair J.; Wang, Jingyang; Moussa, Adel
Organic Process Research and Development, 2010 , vol. 14, # 5 p. 1248 - 1253
反应条件
1.1: n-heptane / 4 h / 90 °C / Inert atmosphere
2.1: n-butyllithium / tetrahydrofuran; hexane / 2.67 h / -80 - -75 °C / Inert atmosphere
2.2: 17 h / -80 - -30 °C / Inert atmosphere
3.1: hydrogenchloride; water / ethanol / 2 h / 5 - 55 °C / Inert atmosphere
3.2: 1 h / 5 - 15 °C / Inert atmosphere
4.1: 1,4-diaza-bicyclo[2.2.2]octane / N,N-dimethyl-formamide / 20 - 36 °C / Inert atmosphere
4.2: 18 h / 20 - 100 °C / Inert atmosphere
5.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 3 h / 20 - 25 °C / Inert atmosphere
5.2: 3 h / 20 - 25 °C / Inert atmosphere
View Scheme
参考文献
Mayes, Benjamin A.; Chaudhuri, Narayan C.; Hencken, Christopher P.; Jeannot, Frederic; Latham, G. Mark; Mathieu, Steven; Mcgarry, F. Patrick; Stewart, Alistair J.; Wang, Jingyang; Moussa, Adel
Organic Process Research and Development, 2010 , vol. 14, # 5 p. 1248 - 1253
反应条件
1.1: hydrogenchloride; water / ethanol / 2 h / 5 - 55 °C / Inert atmosphere
1.2: 1 h / 5 - 15 °C / Inert atmosphere
2.1: 1,4-diaza-bicyclo[2.2.2]octane / N,N-dimethyl-formamide / 20 - 36 °C / Inert atmosphere
2.2: 18 h / 20 - 100 °C / Inert atmosphere
3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 3 h / 20 - 25 °C / Inert atmosphere
3.2: 3 h / 20 - 25 °C / Inert atmosphere
View Scheme
参考文献
Mayes, Benjamin A.; Chaudhuri, Narayan C.; Hencken, Christopher P.; Jeannot, Frederic; Latham, G. Mark; Mathieu, Steven; Mcgarry, F. Patrick; Stewart, Alistair J.; Wang, Jingyang; Moussa, Adel
Organic Process Research and Development, 2010 , vol. 14, # 5 p. 1248 - 1253
反应条件
1.1: 1,4-diaza-bicyclo[2.2.2]octane / N,N-dimethyl-formamide / 20 - 36 °C / Inert atmosphere
1.2: 18 h / 20 - 100 °C / Inert atmosphere
2.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 3 h / 20 - 25 °C / Inert atmosphere
2.2: 3 h / 20 - 25 °C / Inert atmosphere
View Scheme
参考文献
Mayes, Benjamin A.; Chaudhuri, Narayan C.; Hencken, Christopher P.; Jeannot, Frederic; Latham, G. Mark; Mathieu, Steven; Mcgarry, F. Patrick; Stewart, Alistair J.; Wang, Jingyang; Moussa, Adel
Organic Process Research and Development, 2010 , vol. 14, # 5 p. 1248 - 1253
反应条件
1: With water; lithium hydroxide hydrate in tetrahydrofuran
T=20°C; 4 h;
2: With hydrogenchloride in tetrahydrofuran; water
参考文献
Yoshikawa, Kenji; Yokomizo, Aki; Naito, Hiroyuki; Haginoya, Noriyasu; Kobayashi, Shozo; Yoshino, Toshiharu; Nagata, Tsutomu; Mochizuki, Akiyoshi; Osanai, Ken; Watanabe, Kengo; Kanno, Hideyuki; Ohta, Toshiharu
Bioorganic and Medicinal Chemistry, 2009 , vol. 17, # 24 p. 8206 - 8220
