反应详情

Pyrazole-4-boronic acid (19 mg, 0.17 mmol), 4-(5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-2-hydroxy-N-[(6-methyl-pyridin-3-yl)methyl]benzamide (40 mg, 0.085 mmol), K2CO3 (24 mg, 0.17 mmol) and Pd(dppf)Cl2CH2Cl2 (4 mg, 0.005 mmol) are weighed into a sealable tube. The tube is flushed with nitrogen and dioxane-water (4:1, 4 mL) is added. The tube is sealed, placed in an ultrasonic bath under a flow of nitrogen gas for 30 seconds and then placed into an oil bath at 85° C. The reaction is stirred for 28 hours, adding additional portions of boronic acid (10 mg) and catalyst (2 mg) after 2 h and 18 h. The crude mixture is absorbed onto SiO2 and purified by column chromatography, eluting with 1%-10% MeOH/DCM. The product obtained is redissolved in MeOH/DCM (4:1, 10 mL) and 0.1 M MsOH/MeOH (2 eq) is added, the solvents evaporated and the residue taken up in water and lyophillised to afford the title compound as its bis-mesylate salt (38 mg). LCMS: Rt 0.92 min (93.9%) m/z (ESI) 455 (M+H)+.

1. customThe tube is flushed with nitrogen and dioxane-water (4:1, 4 mL)
2. additionis added
3. customThe tube is sealed
4. customplaced into an oil bath at 85° C
5. additionadding additional portions of boronic acid (10 mg) and catalyst (2 mg) after 2 h
6. custom18 h
7. customThe crude mixture is absorbed onto SiO2
8. custompurified by column chromatography
9. washeluting with 1%-10% MeOH/DCM
10. customThe product obtained
11. customthe solvents evaporated