反应详情

温度

100 °C

A mixture of 4-({[2′-fluoro-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine hydrochloride (Example 66, Step 1, 0.12 g, 0.30 mmol), 2-chloro-5-bromopyrimidine (89 mg, 0.45 mmol) and K2CO3 (0.13 g, 0.90 mmol) in DMSO (5 mL) was degassed, purged with N2 and heated at 100° C. overnight. The mixture was allowed to cool to ambient temperature, and was poured into water (50 mL) and extracted with EtOAc. The combined organic extract was washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a yellow solid. The crude product was triturated with hot hexanes containing 1% of MeOH to give 0.142 g (91%) of the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 8.29 (s, 2H), 7.80-7.70 (m, 2H), 7.65-7.55 (m, 1H), 7.50 (d, 2H, J=7.6 Hz), 6.99 (d, 2H, J=8.7 Hz), 4.85-4.75 (m, 2H), 3.88 (d, 2H, J=6.3 Hz), 3.09 (s, 3H), 3.00-2.90 (m, 2H), 2.20-2.05 (m, 1H), 2.00-1.90 (m, 2H), 1.45-1.30 (m, 2H); LRMS (ESI), m/z 520/522 (M+H).

1. customwas degassed
2. custompurged with N2
3. temperatureto cool to ambient temperature
4. additionwas poured into water (50 mL)
5. extractionextracted with EtOAc
6. extractionThe combined organic extract
7. washwas washed with water and brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationthe filtrate was concentrated
11. customto give the crude product as a yellow solid
12. customThe crude product was triturated with hot hexanes containing 1% of MeOH