Dimethylformamide → 5-Bromo-2-fluoro-4-methylbenzaldehyde

Temperature

-70 °C

Diisopropylamine (2.5 mL, 19.1 mmol) was dissolved in THF (24 mL) and the solution was cooled to −70° C., then the solution was added with n-butyllithium (1.57 mol/L hexane solution, 12 mL, 19.1 mmol), followed by stirring for 10 minutes. After warmed to room temperature, the mixture was cooled to −70° C. again and a solution of 2-methyl-4-fluorobromobenzene (3.0 g, 15.9 mmol) in THF (4 mL) was added dropwise thereto. After stirring for 15 minutes, the mixture was added with DMF (1.9 mL, 23.8 mmol) and warmed to 0° C., followed by stirring for 20 minutes. The reaction mixture was added with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to obtain 5-bromo-2-fluoro-4-methylbenzaldehyde as a crude product. In a similar manner to Reference Example 2, 2-amino-6-bromo-7-methylquinazoline (2.0 g, 50%) was obtained using the above-obtained 5-bromo-2-fluoro-4-methylbenzaldehyde. In a similar manner to Reference Example 3 and Reference Example 4, Compound A11 was obtained using the above-obtained 2-amino-6-bromo-7-methylquinazoline.

1. temperatureAfter warmed to room temperature
2. temperaturethe mixture was cooled to −70° C. again
3. stirringAfter stirring for 15 minutes
4. temperaturewarmed to 0° C.
5. stirringby stirring for 20 minutes
6. extractionextracted with ethyl acetate
7. washThe organic layer was washed with saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. customThe solvent was evaporated under reduced pressure

ORD record

ord-34a53519d2a142cfbecb3dfc4616824e

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07906522B2