反应详情

温度

100 °C

5-Bromo-3-methyl-2-methylthio-4(3H)-pyrimidinone (Step 3, 14.77 g, 62.8 mmol), 3-fluoro-4-methoxyphenylboronic acid (20.11 g, 118.3 mmol), Pd2(dba)3 (1.869 g, 2.04 mmol), S-phos ligand (Strem Chemical, 3.45 g, 8.40 mmol) and K3PO4 (42.27 g, 199.1 mmol) were suspended in toluene (200 mL). Ar was bubbled through the solution for 5 min, and the reaction was placed in an oil bath (100° C.) and stirred for 6.25 h, at which time LCMS analysis indicated a complete reaction. The reaction was cooled to RT and allowed to stand overnight. It was diluted with CH2Cl2 (200 mL) and filtered through a 1-inch plug of silica gel which was washed exhaustively with MeOH, EtOAc, and CH2Cl2. (Some solid material stuck in the flask had to be taken up in water and extracted with EtOAc separately). The filtrate (and EtOAc extracts) were all combined and concentrated, resulting in an orange solid. This was treated with hexanes and filtered, and the resultant light yellow solid was washed repeatedly with hexanes and then put on the high vacuum overnight. The title compound was obtained as a light yellow solid. MS (ESI pos. ion) m/z: 281. Calc'd for C13H13FN2O2S: 280.07.

1. customAr was bubbled through the solution for 5 min
2. customthe reaction was placed in an oil bath
3. customa complete reaction
4. temperatureThe reaction was cooled to RT
5. waitto stand overnight
6. filtrationfiltered through a 1-inch plug of silica gel which
7. washwas washed exhaustively with MeOH, EtOAc, and CH2Cl2
8. extractionextracted with EtOAc separately)
9. concentrationconcentrated
10. customresulting in an orange solid
11. filtrationfiltered
12. washthe resultant light yellow solid was washed repeatedly with hexanes
13. customput on the high vacuum overnight