一水合二对甲苯磺酸拉帕替尼合成路线 (共 28 条)
反应条件
1.1: trifluoroacetic acid / toluene / 110 - 115 °C / Molecular sieve; Inert atmosphere 2.1: potassium carbonate / triphenyl-arsane; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 60 - 65 °C / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 3.2: 2 h / 20 - 25 °C 4.1: toluene-4-sulfonic acid / methanol / 1 h / 25 °C 5.1: trichlorophosphate / toluene / 0.17 h / 20 °C / Inert atmosphere 5.2: 3 h / 30 - 75 °C 6.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 7.1: sodium hydroxide / ethyl acetate; water / pH ~ 10 / Inert atmosphere 7.2: 1 h / 40 °C View Scheme
反应条件
1.1: toluene-4-sulfonic acid / methanol / 1 h / 25 °C 2.1: trichlorophosphate / toluene / 0.17 h / 20 °C / Inert atmosphere 2.2: 3 h / 30 - 75 °C 3.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 4.1: sodium hydroxide / ethyl acetate; water / pH ~ 10 / Inert atmosphere 4.2: 1 h / 40 °C View Scheme
反应条件
1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 1.2: 2 h / 20 - 25 °C 2.1: toluene-4-sulfonic acid / methanol / 1 h / 25 °C 3.1: trichlorophosphate / toluene / 0.17 h / 20 °C / Inert atmosphere 3.2: 3 h / 30 - 75 °C 4.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 5.1: sodium hydroxide / ethyl acetate; water / pH ~ 10 / Inert atmosphere 5.2: 1 h / 40 °C View Scheme
反应条件
1.1: potassium carbonate / triphenyl-arsane; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 60 - 65 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 2.2: 2 h / 20 - 25 °C 3.1: toluene-4-sulfonic acid / methanol / 1 h / 25 °C 4.1: trichlorophosphate / toluene / 0.17 h / 20 °C / Inert atmosphere 4.2: 3 h / 30 - 75 °C 5.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 6.1: sodium hydroxide / ethyl acetate; water / pH ~ 10 / Inert atmosphere 6.2: 1 h / 40 °C View Scheme
反应条件
in tetrahydrofuran; water T=60 - 64°C; 1 h; Product distribution / selectivity;
参考文献
WO2006/113649 A1, ;
Page/Page column 48 ;
WO 2006/113649 A1
反应条件
1: acetic acid / 2 h / 115 - 120 °C 2: triethylamine; ethylene glycol dimethyl ether / palladium 10 on activated carbon / methanol / Inert atmosphere 3: triethylamine / methanol / 12 h / Reflux 4: methanol / tetrahydrofuran / 0 - 15 °C 5: methanol / 3 h / Reflux View Scheme
反应条件
1: triethylamine / palladium 10 on activated carbon / ethylene glycol dimethyl ether; methanol / 15 h / 45 - 50 °C / Inert atmosphere 2: triethylamine / methanol / 12 h / Reflux 3: sodium tetrahydroborate / tetrahydrofuran; methanol / 4 h / 10 - 15 °C 4: methanol / 3 h / 25 - 65 °C View Scheme
反应条件
1: acetic acid / toluene / 2 h / Reflux 2: acetic acid / xylene / 10 h / Reflux 3: triethylamine / palladium 10 on activated carbon / ethylene glycol dimethyl ether; methanol / 15 h / 45 - 50 °C / Inert atmosphere 4: triethylamine / methanol / 12 h / Reflux 5: sodium tetrahydroborate / tetrahydrofuran; methanol / 4 h / 10 - 15 °C 6: methanol / 3 h / 25 - 65 °C View Scheme
反应条件
1: acetic acid / xylene / 10 h / Reflux 2: triethylamine / palladium 10 on activated carbon / ethylene glycol dimethyl ether; methanol / 15 h / 45 - 50 °C / Inert atmosphere 3: triethylamine / methanol / 12 h / Reflux 4: sodium tetrahydroborate / tetrahydrofuran; methanol / 4 h / 10 - 15 °C 5: methanol / 3 h / 25 - 65 °C View Scheme
反应条件
1: triethylamine / methanol / 12 h / Reflux 2: methanol / tetrahydrofuran / 0 - 15 °C 3: methanol / 3 h / Reflux View Scheme