Diethyl Ether → N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-acetyl-6-methylpyrimidinamine

Temperature

-78 °C

A solution of N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-carboxy-6-methylpyrimidinamine (3.7 g, 9.8 mmol) in anhydrous THF (25 mL) was cooled with stirring to −78° C. under a nitrogen atmosphere. A solution of methyl lithium in ether (1.4 M, 7 mL, 9.8 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for 1 h. The CeCl3 suspension was transferred via cannula into the reaction mixture and stirring at −78° C. was continued for 5 h. A solution of methyl lithium in ether (1.4 M, 7 mL, 9.8 mmol) was added dropwise and the reaction mixture was then warmed gradually to room temperature over 16 h. After cooling the reaction mixture to −78° C., the reaction was quenched with a 1 N HCl solution and warmed to room temperature. The resulting mixture was extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give an orange yellow oil. Column chromatography (ethyl acetate:hexanes::1:4) afforded the title product as an oil (2.5 g, 68% yield, Rf 0.5): NMR (CDCl3, 300 MHz): 7.55 (d, 1H, J=1), 7.25-7.15 (m, 2H), 6.95 (s, 1H), 4.30-4.10 (m, 1H), 3.90-3.70 (m, 1H), 3.00-2.85 (m, 1H), 2.80-2.05 (m, 6H), 1.35-1.20 (m, 9H); CI-HRMS: Calcd (C18H22BrN3O): 376.1024 (M+H), Found: 376.1042.

1. stirringthe reaction mixture was stirred at −78° C. for 1 h
2. stirringstirring at −78° C.
3. temperaturethe reaction mixture was then warmed gradually to room temperature over 16 h
4. temperatureAfter cooling the reaction mixture to −78° C.
5. customthe reaction was quenched with a 1 N HCl solution
6. temperaturewarmed to room temperature
7. extractionThe resulting mixture was extracted three times with ethyl acetate
8. dry with materialThe combined organic layers were dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give an orange yellow oil

ORD record

ord-6b535c4ec17b496985480bdf766bf88f

Source dataset

uspto-grants-2002_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06342503B1