P-[2-[[4-[(3-氯-4-氟苯基)氨基]-7-[[(3S)-四氢-3-呋喃基]氧基-6-喹唑啉基]氨基]-2-氧代乙基]膦酸二乙酯合成路线 （共 3 条）
反应条件
1: N,N-Dimethylaminoacetaldehyde diethyl acetal With hydrogenchloride in water T=20 - 30°C; Inert atmosphere; 2: Diethyl {[4-(3-Chloro-4-Fluoro-Phenylamino)-7-((S)-Tetrahydrofuran-3-Yloxy)-Quinazolin-6-Ylcarbamoyl]-Methyl}-Phosphonate With lithium chloride; potassium hydroxide in tetrahydrofuran T=-15 - 20°C; 2.5 h; Inert atmosphere; Product distribution / selectivity;
参考文献
RATIOPHARM GMBH; TEVA PHARMACEUTICALS USA, INC.; GIDWANI, Ramesh, Matioram; HIREMATH, Channaveerayya; YADAV, Manoj, Dalsingar; ALBRECHT, Wolfgang; FISCHER, Dirk
Patent: WO2012/121764 A1, 2012 ;
Location in patent: Page/Page column 49-50 ;
反应条件
1,1'-carbonyldiimidazole in DMF (N,N-dimethyl-formamide)
T=20°C; 4 - 5 h;
参考文献
Boehringer ingelheim international GmbH
Patent: US2005/107358 A1, 2005 ;
Location in patent: Page/Page column 5 ;
US 20050107358 A1
反应条件
1: diethyl carboxymethylphosphonate With 1,1'-carbonyldiimidazole
T=20°C;
2: 6-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline in DMF (N,N-dimethyl-formamide)
T=20°C; 4 - 5 h;
参考文献
BOEHRINGER INGELHEIM INTERNATIONAL GMBH; BOEHRINGER INGELHEIM PHARMA GMBH and CO. KG
Patent: WO2004/74263 A1, 2004 ;
Location in patent: Page 15 ;
WO 2004/074263 A1
