Sodium Carbonate → 5-(4-Chloro-2-fluorophenyl)pyrimidin-2-amine

Temperatur

50 °C

To a 500 mL round-bottomed flask were added 5-bromo-2-aminopyrimidine (4.0 g, 23 mmol), 4-chloro-2-fluorophenylboronic acid (3.9 g, 23 mmol), palladium(II)trifluoroacetate (240 mg, 0.72 mmol), and triphenylphoshine (373 mg, 1.40 mmol). The reaction vessel was fitted with a rubber septum, sparged with nitrogen and then charged with sparged toluene (75 mL), ethanol (75 mL), and a 2M solution of sodium carbonate (42 mL, 84 mmol) (solvents were sparged individually nitrogen gas for 30 minutes). The resulting mixture was stirred vigorously and heated at 50° Celsius. After 12 hours, the mixture was cooled to rt and treated with 100 mL of water. The precipitate was isolated via vacuum filtration, and the filtrate extracted with EtOAC. The EtOAc solution was dried, filtered and concentrated to dryness. The resultant solids were recrystallized from IPA (80 mL) to afford title compound (3.8 g, 74%). MS (ESI): mass calcd. for C10H7ClFN3, 223.03; m/z found, 224.0 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.44 (d, J=1.4, 2H), 7.59 (m, 1H), 7.54 (dd, J=10.7, 2.1, 1H), 7.37 (dd, J=8.3, 2.1, 1H), 6.94 (s, 2H).

1. customThe reaction vessel was fitted with a rubber septum
2. customsparged with nitrogen
3. additioncharged with sparged toluene (75 mL), ethanol (75 mL)
4. temperaturethe mixture was cooled to rt
5. customThe precipitate was isolated via vacuum filtration
6. extractionthe filtrate extracted with EtOAC
7. dry with materialThe EtOAc solution was dried
8. filtrationfiltered
9. concentrationconcentrated to dryness
10. customThe resultant solids were recrystallized from IPA (80 mL)

ORD-Eintrag

ord-ec10fda641864c96b7265cbcc79d29e7

Quelldatensatz

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09079866B2