Water → HCID 67403343, compound

2-Amino-5-fluoropyridine (2.5 g) and 2-bromo-4′-cyanoacetophenone (5.0 g) were dissolved in ethanol (100 mL), and sodium hydrogencarbonate (1.9 g) was added to the solution, followed by refluxing for 16 hours. Water (10 mL) was added to the reaction mixture. After the reaction mixture had been left to cool, the precipitated matter was recovered through filtration and dried, to thereby yield 4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)benzonitrile (2.1 g). Subsequently, the thus-obtained 4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)benzonitrile was dissolved in anhydrous tetrahydrofuran solution (30 mL), and diisobutylaluminum hydride (9.0 mL, 0.93M hexane solution) was added dropwise to the solution at −78° C., followed by stirring under a stream of argon at room temperature for 2 hours. Saturated aqueous ammonium chloride solution (10 mL) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. Anhydrous magnesium sulfate and diethyl ether were added to the resultant mixture, followed by further stirring for 1 hour. The solvent was evaporated, and the residue was purified, to thereby yield 4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)benzaldehyde (0.6 g). Subsequently, this product was dissolved in anhydrous tetrahydrofuran solution (30 mL), and methyl magnesium bromide (0.78 mL, 3M hexane solution) was added dropwise to the mixture under a stream of argon at −78° C., followed by stirring under ice cooling for 15 minutes and then at room temperature for 3 hours. Saturated aqueous ammonium chloride solution (10 mL) was added dropwise to the reaction mixture, followed by stirring at room temperature for 1 hour. The mixture was extracted with dichloromethane-methanol, and purified through silica gel chromatography (dichloromethane:methanol=95:5), to thereby yield 1-[4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)phenyl]-1-ethanol (530 mg). The thus-obtained 1-[4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)phenyl]-1-ethanol (530 mg) was dissolved in chloroform solution (50 mL), and manganese dioxide (721 mg) was added to the solution, followed by refluxing for 4 hours. After the reaction mixture had been filtered through Celite, the filtrate was concentrated, and the residue was purified through silica gel chromatography (dichloromethane:methanol=98:2), to thereby yield the title compound (410 mg).

1. temperatureby refluxing for 16 hours
2. waitAfter the reaction mixture had been left
3. temperatureto cool
4. filtrationthe precipitated matter was recovered through filtration
5. customdried
6. dissolutionSubsequently, the thus-obtained 4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)benzonitrile was dissolved in anhydrous tetrahydrofuran solution (30 mL)
7. additiondiisobutylaluminum hydride (9.0 mL, 0.93M hexane solution) was added dropwise to the solution at −78° C.
8. additionSaturated aqueous ammonium chloride solution (10 mL) was added dropwise to the reaction mixture
9. stirringthe mixture was stirred at room temperature for 1 hour
10. additionAnhydrous magnesium sulfate and diethyl ether were added to the resultant mixture
11. stirringby further stirring for 1 hour
12. customThe solvent was evaporated
13. customthe residue was purified
14. dissolutionSubsequently, this product was dissolved in anhydrous tetrahydrofuran solution (30 mL)
15. additionmethyl magnesium bromide (0.78 mL, 3M hexane solution) was added dropwise to the mixture under a stream of argon at −78° C.
16. stirringby stirring under ice cooling for 15 minutes
17. waitat room temperature for 3 hours
18. additionSaturated aqueous ammonium chloride solution (10 mL) was added dropwise to the reaction mixture
19. stirringby stirring at room temperature for 1 hour
20. extractionThe mixture was extracted with dichloromethane-methanol
21. custompurified through silica gel chromatography (dichloromethane:methanol=95:5)
22. dissolutionThe thus-obtained 1-[4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)phenyl]-1-ethanol (530 mg) was dissolved in chloroform solution (50 mL)
23. additionmanganese dioxide (721 mg) was added to the solution
24. temperatureby refluxing for 4 hours
25. filtrationAfter the reaction mixture had been filtered through Celite
26. concentrationthe filtrate was concentrated
27. customthe residue was purified through silica gel chromatography (dichloromethane:methanol=98:2)

ORD record

ord-eebb08a964444ce7a78c796786d32d12

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08022075B2