反应详情

2-n-Propyl-5-(2-aminoethyl)-3-[2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methylimidazole (1.01g) is dissolved in tetrahydrofuran (10 ml), and thereto is added ethyl glyoxylate hydrate (195 mg), and the mixture is stirred at room temperature overnight. The mixture is heated at 50° C. for 30 minutes, and after cooling, 7% hydrochloric acid-methanol solution (3 ml) and chloroform (10 ml) are added to the mixture, which is refluxed for 20 minutes. The mixture is evaporated under reduced pressure to remove the solvent, and the resulting residue is dissolved in chloroform (30 ml). To the mixture are added acetic anhydride (290 mg) and a solution of sodium hydrogen carbonate (1.2 g) in water (20 ml), and the mixture is stirred at room temperature overnight. The mixture is acidified with citric acid, and extracted with chloroform. The extract is washed with water, dried, and evaporated. To the residue are added fumaric acid (100 mg) and ethanol (35 ml), and the mixture is refluxed for 5 hours. Then, the reaction mixture is evaporated under reduced pressure, and the residue is recrystallized from methanol/ether to give ethyl 2-n-propyl-5-acetyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-4-carboxylate 1/2 fumarate (728 mg).

1. temperatureThe mixture is heated at 50° C. for 30 minutes
2. temperatureafter cooling
3. temperatureis refluxed for 20 minutes
4. customThe mixture is evaporated under reduced pressure
5. customto remove the solvent
6. dissolutionthe resulting residue is dissolved in chloroform (30 ml)
7. additionTo the mixture are added acetic anhydride (290 mg)
8. stirringa solution of sodium hydrogen carbonate (1.2 g) in water (20 ml), and the mixture is stirred at room temperature overnight
9. extractionextracted with chloroform
10. washThe extract is washed with water
11. customdried
12. customevaporated
13. additionTo the residue are added fumaric acid (100 mg) and ethanol (35 ml)
14. temperaturethe mixture is refluxed for 5 hours
15. customThen, the reaction mixture is evaporated under reduced pressure
16. customthe residue is recrystallized from methanol/ether