1: 4-bromo-but-2-enoyl chloride; 6-amino-4-(3-chloro-4-fluoro-phenylamino)-7-ethoxy-quinoline-3-carbonitrile With N-ethyl-N,N-diisopropylamine in tetrahydrofuran 2: dimethyl amine in tetrahydrofuran T=20°C; Further stages.;

1.1: 95 percent / propan-2-ol / 3.5 h / Heating 2.1: 89 percent / Fe; aq. NH4Cl / methanol / 4 h / Heating 3.1: iPr2NEt / tetrahydrofuran 3.2: tetrahydrofuran / 20 °C View Scheme

1.1: 65 percent / AcOH / 0.5 h / Heating 2.1: LiCl / dimethylformamide / 12 h / Heating 3.1: K2CO3 / dimethylformamide / 5 h / Heating 4.1: KMnO4; MgSO4 / H2O / 1.5 h / Heating 5.1: 71 percent / aq. H2SO4 / 1 h / 110 - 112 °C 6.1: 80 percent / toluene / 16 h / Heating 7.1: 76 percent / Dowtherm / 1.25 h / 256 °C 8.1: 87 percent / POCl3 / 2.5 h / Heating 9.1: 95 percent / propan-2-ol / 3.5 h / Heating 10.1: 89 percent / Fe; aq. NH4Cl / methanol / 4 h / Heating 11.1: iPr2NEt / tetrahydrofuran 11.2: tetrahydrofuran / 20 °C View Scheme

1.1: 80 percent / toluene / 16 h / Heating 2.1: 76 percent / Dowtherm / 1.25 h / 256 °C 3.1: 87 percent / POCl3 / 2.5 h / Heating 4.1: 95 percent / propan-2-ol / 3.5 h / Heating 5.1: 89 percent / Fe; aq. NH4Cl / methanol / 4 h / Heating 6.1: iPr2NEt / tetrahydrofuran 6.2: tetrahydrofuran / 20 °C View Scheme

1.1: LiCl / dimethylformamide / 12 h / Heating 2.1: K2CO3 / dimethylformamide / 5 h / Heating 3.1: KMnO4; MgSO4 / H2O / 1.5 h / Heating 4.1: 71 percent / aq. H2SO4 / 1 h / 110 - 112 °C 5.1: 80 percent / toluene / 16 h / Heating 6.1: 76 percent / Dowtherm / 1.25 h / 256 °C 7.1: 87 percent / POCl3 / 2.5 h / Heating 8.1: 95 percent / propan-2-ol / 3.5 h / Heating 9.1: 89 percent / Fe; aq. NH4Cl / methanol / 4 h / Heating 10.1: iPr2NEt / tetrahydrofuran 10.2: tetrahydrofuran / 20 °C View Scheme

1.1: 62 percent / TFA anhydride; NH4NO2 2.1: 87 percent / POCl3 / 2.5 h / Heating 3.1: 95 percent / propan-2-ol / 3.5 h / Heating 4.1: 89 percent / Fe; aq. NH4Cl / methanol / 4 h / Heating 5.1: iPr2NEt / tetrahydrofuran 5.2: tetrahydrofuran / 20 °C View Scheme

1.1: KMnO4; MgSO4 / H2O / 1.5 h / Heating 2.1: 71 percent / aq. H2SO4 / 1 h / 110 - 112 °C 3.1: 80 percent / toluene / 16 h / Heating 4.1: 76 percent / Dowtherm / 1.25 h / 256 °C 5.1: 87 percent / POCl3 / 2.5 h / Heating 6.1: 95 percent / propan-2-ol / 3.5 h / Heating 7.1: 89 percent / Fe; aq. NH4Cl / methanol / 4 h / Heating 8.1: iPr2NEt / tetrahydrofuran 8.2: tetrahydrofuran / 20 °C View Scheme

1.1: 95 percent / propan-2-ol / 3.5 h / Heating 2.1: 89 percent / Fe; aq. NH4Cl / methanol / 4 h / Heating 3.1: iPr2NEt / tetrahydrofuran 3.2: tetrahydrofuran / 20 °C View Scheme

1.1: 87 percent / POCl3 / 2.5 h / Heating 2.1: 95 percent / propan-2-ol / 3.5 h / Heating 3.1: 89 percent / Fe; aq. NH4Cl / methanol / 4 h / Heating 4.1: iPr2NEt / tetrahydrofuran 4.2: tetrahydrofuran / 20 °C View Scheme

1.1: 71 percent / aq. H2SO4 / 1 h / 110 - 112 °C 2.1: 80 percent / toluene / 16 h / Heating 3.1: 76 percent / Dowtherm / 1.25 h / 256 °C 4.1: 87 percent / POCl3 / 2.5 h / Heating 5.1: 95 percent / propan-2-ol / 3.5 h / Heating 6.1: 89 percent / Fe; aq. NH4Cl / methanol / 4 h / Heating 7.1: iPr2NEt / tetrahydrofuran 7.2: tetrahydrofuran / 20 °C View Scheme