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: N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl]quinazoline-4-amine hydrochloride With sodium hydroxide in water; ethyl acetate pH=~ 10; Inert atmosphere; 2: toluene-4-sulfonic acid in N,N-dimethyl-formamide T=40°C; 1 h;
参考文献
EP2468745 A1, ;
Page/Page column 13-14 ;
反应条件
1: N-{3-chloro-4-[(3-fluoro-benzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl]quinazoline-4-amine hydrochloride With sodium hydroxide in water; ethyl acetate pH=10; Inert atmosphere; 2: toluene-4-sulfonic acid in N,N-dimethyl-formamide T=40°C; 1 h;
参考文献
US2012/245350 A1, ;
Page/Page column 9 ;
反应条件
1: 2-(methanesulphonyl)ethylamine hydrochloride; 5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde With acetic acid; N-ethyl-N,N-diisopropylamine in tetrahydrofuran; N,N-dimethyl-formamide T=35°C; 1 h; 2: With sodium tris(acetoxy)borohydride in tetrahydrofuran; N,N-dimethyl-formamide T=20 - 25°C; 2 h; 3: toluene-4-sulfonic acid
参考文献
WO2010/17387 A2, ;
Page/Page column 29-30 ;
反应条件
1: 1-(methylsulfonyl)eth-2-ylamine; 5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde in methanol; dichloromethane T=20°C; 2: With hydrogen in methanol; dichloromethane Inert atmosphere; 3: toluene-4-sulfonic acid in methanol; dichloromethane
参考文献
WO2012/83440 A1, ;
Page/Page column 13-14 ;
反应条件
1: N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(5-((2-(methylsulfonyl)ethylimino)methyl)furan-2-yl)quinazolin-4-amine With sodium tris(acetoxy)borohydride in tetrahydrofuran T=20 - 25°C; 1 h; 2: With water; sodium hydroxide in tetrahydrofuran 3: toluene-4-sulfonic acid in tetrahydrofuran 3 h;
参考文献
WO2013/80218 A1, ;
Page/Page column 12; 17 ;
反应条件
in methanol T=45 - 65°C; Reflux;
参考文献
WO2010/61400 A1, ;
Page/Page column 17 ;
反应条件
1: 5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde 4-methylbenzenesulfonate; 2-(methanesulphonyl)ethylamine hydrochloride With acetic acid; N-ethyl-N,N-diisopropylamine in methanol T=5 - 10°C; 1 h; 2: With sodium cyanoborohydride in methanol T=5 - 10°C; 19 h; 3: toluene-4-sulfonic acid Product distribution / selectivity;
参考文献
WO2010/17387 A2, ;
Page/Page column 23 ;
反应条件
1: triethylamine; ethylene glycol dimethyl ether / palladium 10 on activated carbon / methanol / Inert atmosphere 2: triethylamine / methanol / 12 h / Reflux 3: methanol / tetrahydrofuran / 0 - 15 °C 4: methanol / 3 h / Reflux View Scheme
反应条件
1: iodine cloride; acetic acid / 3 h / 25 - 35 °C 2: 2 h / 70 - 75 °C 3: acetic acid / 2 h / 115 - 120 °C 4: triethylamine; ethylene glycol dimethyl ether / palladium 10 on activated carbon / methanol / Inert atmosphere 5: triethylamine / methanol / 12 h / Reflux 6: methanol / tetrahydrofuran / 0 - 15 °C 7: methanol / 3 h / Reflux View Scheme
反应条件
1: 2 h / 70 - 75 °C 2: acetic acid / 2 h / 115 - 120 °C 3: triethylamine; ethylene glycol dimethyl ether / palladium 10 on activated carbon / methanol / Inert atmosphere 4: triethylamine / methanol / 12 h / Reflux 5: methanol / tetrahydrofuran / 0 - 15 °C 6: methanol / 3 h / Reflux View Scheme
