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0 °C

A three-neck 2 L flask equipped with an overhead stirrer, a thermocouple, a condenser and a nitrogen inlet was charged with 6-(benzylthio)-1-chloroisoquinoline (23 g, 80 mmol), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (22.1 g, 101 mmol), potassium phosphate (51.2 g, 241 mmol) and Amphos (2.85 g, 4.02 mmol) in that order. The flask was evacuated. In a separate flask was charged with dioxane (230 mL) and water (57.5 mL). The solvent solution was sparged with nitrogen and charged to the reaction flask. The reaction flask was purged with nitrogen and warmed to reflux. After 1 hr, the reaction was complete according to LC/MS. The whole was cooled to 0° C., charged with DCM and water. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated down to afford black oil. Isopropanol was added into the black oil and the whole was concentrated again to fully remove DCM and dioxane. The black residue was charged with 200 mL of isopropanol. The product crystallized out of solution. The slurry was stirred for 2 hrs at RT and cooled to 0° C. for 1 hr. The product was filtered off, washed with 30% isopropanol/heptane solution, and dried under vacuum with a nitrogen sweep. The product was obtained as gray solids (24.1 g, 70.4%; >99% purity via LC/MS at 215 nm). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=8.58 (d, J=5.8 Hz, 1H), 7.66 (d, J=1.8 Hz, 1H), 7.56-7.47 (m, 3H), 7.45-7.26 (m, 8H), 4.31 (s, 2H), 3.76 (s, 3H); m/z (ESI) 426.2 (M+H)+.

1. customA three-neck 2 L flask equipped with an overhead stirrer
2. customThe flask was evacuated
3. additionIn a separate flask was charged with dioxane (230 mL) and water (57.5 mL)
4. customThe solvent solution was sparged with nitrogen
5. additioncharged to the reaction flask
6. customThe reaction flask was purged with nitrogen
7. temperaturewarmed to reflux
8. additioncharged with DCM and water
9. customThe organic layer was separated
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated down
13. customto afford black oil
14. concentrationthe whole was concentrated again to fully remove DCM and dioxane
15. additionThe black residue was charged with 200 mL of isopropanol
16. customThe product crystallized out of solution
17. temperaturecooled to 0° C. for 1 hr
18. filtrationThe product was filtered off
19. washwashed with 30% isopropanol/heptane solution
20. customdried under vacuum with a nitrogen sweep
21. customThe product was obtained as gray solids (24.1 g, 70.4%; >99% purity via LC/MS at 215 nm)