1: (E)-4-(dimethylamino)but-2-enoic acid hydrochloride salt With oxalyl dichloride; N,N-dimethyl-formamide in tetrahydrofuran T=0 - 30°C; 2 h; 2: 6-amino-4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-7-ethoxy-quinoline-3-carbonitrile in tetrahydrofuran; 1-methyl-pyrrolidin-2-one T=0 - 5°C; 3 - 16 h;

1: (E)-4-(dimethylamino)but-2-enoic acid hydrochloride salt With oxalyl dichloride; N,N-dimethyl-formamide in tetrahydrofuran T=0 - 30°C; 2.25 h; 2: 6-amino-4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-7-ethoxy-quinoline-3-carbonitrile in tetrahydrofuran; 1-methyl-pyrrolidin-2-one T=0 - 10°C; 20.5 h;

1: With 1-methyl-pyrrolidin-2-one in tetrahydrofuran 3 - 16 h; 2: With water in tetrahydrofuran T=40°C; 3: With sodium hydroxide in tetrahydrofuran; water pH=10 - 11;

in tetrahydrofuran; 1-methyl-pyrrolidin-2-one T=0 - 5°C; 5 h; Product distribution / selectivity;

pyridine hydrochloride in isopropyl alcohol Heating;

1: N,N-Dimethylaminoacetaldehyde diethyl acetal With hydrogenchloride; water T=0 - 40°C; Inert atmosphere; 2: diethyl 2-[4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-ylamino]-2-oxoethylphosphonate With sodium ethanolate; lithium chloride in ethanol; water T=-20°C; 3 h;

1: 7.97 g / 1-methyl-pyrrolidin-2-one / 2.5 h / 0 - 20 °C 2: 85 percent / pyridine hydrochloride / propan-2-ol / Heating View Scheme

1: iron; AcOH; NaOAc / methanol / Heating 2: 7.97 g / 1-methyl-pyrrolidin-2-one / 2.5 h / 0 - 20 °C 3: 85 percent / pyridine hydrochloride / propan-2-ol / Heating View Scheme

1: 7.97 g / 1-methyl-pyrrolidin-2-one / 2.5 h / 0 - 20 °C 2: 85 percent / pyridine hydrochloride / propan-2-ol / Heating View Scheme

1.1: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 12 h / 50 - 60 °C 2.1: iron; ammonium chloride / ethanol; water / 1 h / |Reflux 3.1: methanesulfonic acid / ethanol / 2 h / |Reflux 4.1: hydrogenchloride; water / |Reflux 5.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 5 h / 40 °C 6.1: hydrogenchloride; water / 0 - 40 °C / |Inert atmosphere 6.2: 3 h / -20 °C View Scheme