in acetone T=0 - 33°C; 6 h; Reflux;

1: 1-methyl-2-[N-(4-amidinophenyl)aminomethyl]benzimidazol-5-ylcarboxylic acid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)amide With potassium carbonate in water; acetone T=5°C; 0.5 h; 2: chloroformic acid n-hexyl ester in water; acetone T=5°C; 1 h; 3: methanesulfonic acid in water; acetone 1 h; Reflux; Product distribution / selectivity;

1.1: ethyl acetate / 2 h / 20 - 65 °C 1.2: 0.75 h / 40 °C 2.1: sodium hydroxide / water; acetic acid n-butyl ester / 50 °C 2.2: 2 h / 40 °C 3.1: acetone / 6 h / 0 - 33 °C / Reflux View Scheme

1.1: thionyl chloride / N,N-dimethyl-formamide / 0.75 h / Reflux 1.2: 20 - 60 °C 2.1: ammonium formate / palladium on activated charcoal / ethanol / 3 h / Reflux 3.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 1 h / Reflux 3.2: 10 h / Reflux 4.1: hydrogenchloride; toluene-4-sulfonic acid / ethanol / 48 h / 20 °C 4.2: 10 - 20 °C 4.3: 0.75 h / 50 °C 5.1: potassium carbonate / water; acetone / 0.5 h / 5 °C 5.2: 1 h / 50 °C 5.3: 1 h / Reflux View Scheme

1: 1-methyl-2-[N-(4-amidinophenyl)aminomethyl]benzimidazol-5-ylcarboxylic acid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)amide With potassium carbonate in water; acetone T=5°C; 0.5 h; 2: chloroformic acid n-hexyl ester in water; acetone T=50°C; 1 h; 3: methanesulfonic acid in acetone 1 h; Reflux; Product distribution / selectivity;

1.1: water / 4 h / Reflux 1.2: 20 °C / pH 2 2.1: thionyl chloride / N,N-dimethyl-formamide / 0.75 h / Reflux 2.2: 20 - 60 °C 3.1: ammonium formate / palladium on activated charcoal / ethanol / 3 h / Reflux 4.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 1 h / Reflux 4.2: 10 h / Reflux 5.1: hydrogenchloride; toluene-4-sulfonic acid / ethanol / 48 h / 20 °C 5.2: 10 - 20 °C 5.3: 0.75 h / 50 °C 6.1: potassium carbonate / water; acetone / 0.5 h / 5 °C 6.2: 1 h / 50 °C 6.3: 1 h / Reflux View Scheme

1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 2 h / 50 - 55 °C 1.2: 50 h / 50 - 65 °C 2.1: CaCl2x2H2O / ethanol / 0.33 h 2.2: 13 h / 0 - 30 °C 2.3: 10.5 h / 0 - 35 °C 3.1: potassium carbonate / acetonitrile; water / 0.25 h / 12 - 18 °C 3.2: 14.42 h / 12 - 20 °C 4.1: ethyl acetate; ethanol / 8 h / 25 - 35 °C View Scheme

1.1: potassium iodide; sodium hydrogencarbonate; tetrabutylammomium bromide / water / 24 h / 90 - 95 °C 1.2: 0.33 h / 20 - 30 °C / pH 7.5 1.3: 3 h / 20 - 30 °C / pH 2.5 2.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 2 h / 50 - 55 °C 2.2: 50 h / 50 - 65 °C 3.1: CaCl2x2H2O / ethanol / 0.33 h 3.2: 13 h / 0 - 30 °C 3.3: 10.5 h / 0 - 35 °C 4.1: potassium carbonate / acetonitrile; water / 0.25 h / 12 - 18 °C 4.2: 14.42 h / 12 - 20 °C 5.1: ethyl acetate; ethanol / 8 h / 25 - 35 °C View Scheme

1.1: CaCl2x2H2O / ethanol / 0.33 h 1.2: 13 h / 0 - 30 °C 1.3: 10.5 h / 0 - 35 °C 2.1: potassium carbonate / acetonitrile; water / 0.25 h / 12 - 18 °C 2.2: 14.42 h / 12 - 20 °C 3.1: ethyl acetate; ethanol / 8 h / 25 - 35 °C View Scheme

1.1: acetic acid / acetic acid / 88 °C 2.1: thionyl chloride / N,N-dimethyl-formamide / 0.75 h / Reflux 2.2: 20 - 60 °C 3.1: ammonium formate / palladium on activated charcoal / ethanol / 3 h / Reflux 4.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 1 h / Reflux 4.2: 10 h / Reflux 5.1: hydrogenchloride; toluene-4-sulfonic acid / ethanol / 48 h / 20 °C 5.2: 10 - 20 °C 5.3: 0.75 h / 50 °C 6.1: potassium carbonate / water; acetone / 0.5 h / 5 °C 6.2: 1 h / 50 °C 6.3: 1 h / Reflux View Scheme