反应详情

温度

96 °C

To a 2 mL vial were added 1-methyl-3-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (171 mg, 0.39 mmol), 6-tert-Butyl-2-(3-chloro-2-hydroxymethyl-phenyl)-8-fluoro-2H-phthalazin-1-one (100 mg, 0.28 mmol), Potassium carbonate (76.6 mg, 0.55 mmol), tricyclohexylphosphine (4.7 mg, 16.6 μmol) and Pd(dba)2 (4.78 mg, 8.31 μmol). The vial was evacuated and backfilled with Nitrogen. This sequence was repeated three times. Then, 20% aqueous 1,4-dioxane, (1.5 ml) was added to the reaction mixture by syringe. The resulting mixture was heated to 96° C. for gentle reflux and stirred for 5 hr. After cooling down to room temperature, DCM (1 mL) and trithiocyanuric acid trisodium salt, 15% aqueous solution (1 ml) were added to the reaction mixture, then the resulting solution was stirred at 40° C. for 4 hr and additional for 4 hr after addition of 20 mg of activated carbon, then filtered through Celite pad and washed with DCM. DCM layer was collected by phase separation, and the aqueous layer was extracted with additional DCM. The combined organics were diluted with IPA, and DCM was distilled out completely. The desired product was crystallized out from IPA, collected by filtration and washed with IPA. The filter cake was dried under vacuum oven at 50° C. to afford 120 mg of the title compound (68% isolated yield) as a yellow solid. MS (ESI) 640 (M+H)+.

1. customThe vial was evacuated
2. additionThen, 20% aqueous 1,4-dioxane, (1.5 ml) was added to the reaction mixture by syringe
3. temperaturefor gentle reflux
4. temperatureAfter cooling down to room temperature
5. additionDCM (1 mL) and trithiocyanuric acid trisodium salt, 15% aqueous solution (1 ml) were added to the reaction mixture
6. stirringthe resulting solution was stirred at 40° C. for 4 hr and additional for 4 hr
7. additionafter addition of 20 mg of activated carbon
8. filtrationfiltered through Celite pad
9. washwashed with DCM
10. customDCM layer was collected by phase separation
11. extractionthe aqueous layer was extracted with additional DCM
12. additionThe combined organics were diluted with IPA, and DCM
13. distillationwas distilled out completely
14. customThe desired product was crystallized out from IPA
15. filtrationcollected by filtration
16. washwashed with IPA
17. customThe filter cake was dried under vacuum oven at 50° C.