1-methyl-2-methylsulfanyl-4,5-dihydroimidazole

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 35.7 g methyl nitroacetate was added slowly to a refluxing mixture of 39.0 g of 1A and 300 ml of isopropyl alcohol. The mixture then was refluxed for 1 hour with provision to remove the methyl mercaptan by-product. The mixture was cooled and filtered to give the methyl ester of (1-methyl-2-imidazolidinylidene)nitroacetic acid (1B) as a solid, m.p.: 214°-217° (with decomposition). The mixture then was refluxed for 1 hour with provision to remove the methyl mercaptan by-product The mixture was cooled filtered

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 19.5 g of 1A, 17.8 g of methyl nitroacetate and a small amount of zinc chloride were mixed and the mixture was heated to 100°-105°. After 30 minutes, the solid reaction mixture was washed with ether, then with hot methanol. The mixture was filtered to give the methyl ester of (1-methyl-2-imidazolidinylidene)nitroacetic acid (1B) as a tan solid, m.p.: 209°-210°. the mixture was heated to 100°-105° the solid reaction mixture was washed with ether The mixture was filtered

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of [4-(aminomethyl)phenyl]-N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}carboxamide (74 mg, 0.195 mmol), 1-methyl-2-methylthio-2-imidazoline (25 mg, 0.195 mmol), NEt3 (2 mL) and pyridine (5 mL) was stirred at 80° C. overnight, concentrated and HPLC (C18 reversed phase)eluting with 0.1% TFA in H2O/CH3CN gave N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}(4-{[(1-methyl(2-imidazolin-2-yl))amino]methyl}phenyl)carboxamide (52 mg, 65%). MS found for C24H23ClN6O2 (M+H)+: 463. concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Methyl-N-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)-hydrazine is prepared according to Step B of Example 25 using 1-methyl-2-methylsulfanyl-4,5-dihydro-1H-imidazole and methyl hydrazine.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Methyl-N-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)-hydrazine is prepared according to Step B of Example 25 using 1-methyl-2-methylsulfanyl-4,5-dihydro-1H-imidazole and methyl hydrazine.

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of [4-(aminomethyl)phenyl]-N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}carboxamide (74 mg, 0.195 mmol), 1-methyl-2-methylthio-2-imidazoline (25 mg, 0.195 mmol), NEt3 (2 mL) and pyridine (5 mL) was stirred at 80° C. overnight, concentrated and HPLC (C18 reversed phase) eluting with 0.1% TFA in H2O/CH3CN gave N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}(4-{[(1-methyl(2-imidazolin-2-yl))amino]methyl}phenyl)carboxamide (52 mg, 65%). MS found for C24H23ClN6O2 (M+H)+: 463. concentrated HPLC (C18 reversed phase) eluting with 0.1% TFA in H2O/CH3CN

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Methyl-N-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)-hydrazine is prepared according to Step B of Example 25 using 1-methyl-2-methylsulfanyl-4,5-dihydro-1H-imidazole and methyl hydrazine.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 19.5 g of 1A, 17.8 g of methyl nitroacetate and a small amount of zinc chloride were mixed and the mixture heated to 100°-105°. After 30 minutes, the solid reaction mixture was washed with ether, then with hot methanol. The mixture then was filtered to give the methyl ester of (1-methyl-2-imidazolidinylidene)nitroacetic acid (1B) as a tan solid, m.p.: 209°-210°. the mixture heated to 100°-105° the solid reaction mixture was washed with ether The mixture then was filtered

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 19.5 g of 1A, 17.8 g of methyl nitroacetate and a small amount of zinc chloride were mixed and the mixture heated to 100°-105°. After 30 minutes, the solid reaction mixture was washed with ether, then with hot methanol. The mixture then was filtered to give the methyl ester of (1-methyl-2-imidazolidinylidene)nitroacetic acid (1B) as a tan solid, m.p.: 209°-210°. the mixture heated to 100°-105° the solid reaction mixture was washed with ether The mixture then was filtered

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of [4-(aminomethyl)phenyl]-N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}carboxamide (74 mg, 0.195 mmol), 1-methyl-2-methylthio-2-imidazoline (25 mg, 0.195 mmol), NEt3 (2 mL) and pyridine (5 mL) was stirred at 80° C. overnight, concentrated and HPLC (C18 reversed phase) eluting with 0.1% TFA in H2O/CH3CN gave N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}(4-{[(1-methyl(2-imidazolin-2-yl))amino]methyl}phenyl)carboxamide (52 mg, 65%). MS found for C24H23ClN6O2 (M+H)+: 463. concentrated HPLC (C18 reversed phase) eluting with 0.1% TFA in H2O/CH3CN

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of [4-(aminomethyl)phenyl]-N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}carboxamide (74 mg, 0.195 mmol), 1-methyl-2-methylthio-2-imidazoline (25 mg, 0.195 mmol), NEt3 (2 mL) and pyridine (5 mL) was stirred at 80° C. overnight, concentrated and HPLC (C18 reversed phase) eluting with 0.1% TFA in H2O/CH3CN gave N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}(4-{[(1-methyl(2-imidazolin-2-yl))amino]methyl}phenyl)carboxamide (52 mg, 65%). MS found for C24H23ClN6O2 (M+H)+: 463. concentrated HPLC (C18 reversed phase) eluting with 0.1% TFA in H2O/CH3CN