反应详情

温度

150 °C

To 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetic acid from Example 33 step A (1 g, 5.23 mmol) and 2-amino-3-methoxybenzoic acid (875 mg, 5.23 mmol) in pyridine (15 mL) was added triphenyl phosphite (1.51 mL, 5.75 mmol) and the mixture was heated in a microwave synthesizer at 150° C. for 10 min. The mixture was allowed to cool to rt and then ethyl 3-aminopropanoate hydrochloride (883 mg, 5.75 mmol) was added. The mixture was heated in a microwave synthesizer at 190° C. for 4 min and then concentrated under reduced pressure. THF (10 mL) and sodium ethoxide (21% in EtOH, 4 mL) were added, and the mixture was stirred at 60° C. for 0.5 h. The mixture was allowed to cool and concentrated under reduced pressure. The residue was dissolved in water and the pH was adjusted to <4 by addition of 4 N HCl. The precipitate was collected by filtration, washed with water, and dried on the funnel to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-methoxyquinazolin-4-ol (1.19 g, 71%). LC-MS (ESI) m/z 322 (M+H)+.

1. temperatureto cool to rt
2. temperatureThe mixture was heated in a microwave synthesizer at 190° C. for 4 min
3. concentrationconcentrated under reduced pressure
4. additionTHF (10 mL) and sodium ethoxide (21% in EtOH, 4 mL) were added
5. temperatureto cool
6. concentrationconcentrated under reduced pressure
7. dissolutionThe residue was dissolved in water
8. additionthe pH was adjusted to <4 by addition of 4 N HCl
9. filtrationThe precipitate was collected by filtration
10. washwashed with water
11. customdried on the funnel