反应详情

温度

100 °C

Methyl 4-chloro-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylate (50 mg, 0.121 mmole), 2-fluoro-4-(tributylstannyl)pyridine (61 mg, 0.158 mmole), and bis(tri-t-butylphosphine)palladium(0) (6 mg, 0.012 mmole) were combined in a screw cap vial. To this was added 1,4-dioxane (0.5 mL). N2 was bubbled through the mixture for 10 seconds. The vial was capped then heated to 100° C. After stirring overnight the mixture was cooled to RT. Excess QuadraPure was added and stirring continued at RT. After stirring 6 hr the mixture was filtered washing with EtOAc and concentrated. The residue was taken up in 1 mL THF. To this was added KOTMS (47 mg, 0.366 mmole) at RT. After 3 hr the mixture was concentrated. The residue was taken up in Et2O. The resulting off-white solid (53 mg, 88%) was collected by filtration washing with Et2O and dried in vacuo. 1H NMR (400 MHz, DMSO): δ 8.39 (d, J=5.1 Hz, 1 H); 8.35 (d, J=5.9 Hz, 1 H); 7.95 (d, J=5.1 Hz, 1 H); 7.63 (d, J=6.3 Hz, 2 II); 7.21 (d, J=8.4 Hz, 2 H); 7.04 (s, 1 H); 6.95 (d, J=8.8 Hz, 2 H); 5.12-5.05 (m, 2 H); 4.39-4.33 (m, 2 H).

1. customcap vial
2. customN2 was bubbled through the mixture for 10 seconds
3. customThe vial was capped
4. temperaturewas cooled to RT
5. additionExcess QuadraPure was added
6. stirringstirring
7. customcontinued at RT
8. stirringAfter stirring 6 hr the mixture
9. filtrationwas filtered
10. washwashing with EtOAc
11. concentrationconcentrated
12. concentrationAfter 3 hr the mixture was concentrated
13. filtrationThe resulting off-white solid (53 mg, 88%) was collected by filtration
14. washwashing with Et2O
15. customdried in vacuo