反应详情

温度

125 °C

Into a microwave vial containing a mixture of 4-bromo-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)thiazole (0.030 g, 0.061 mmol) and 4-(hydroxymethyl)phenylboronic acid (0.026 g, 0.17 mmol) was added 1M aqueous NaHCO3 (0.15 mL, 0.15 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II)dichloride (0.0021 g, 0.003 mmol) and 1,2-dimethoxyethane (0.60 mL). The vial was flushed with nitrogen gas and the reaction mixture was heated at 125° C. in a Biotage Microwave reactor for 30 minutes. Upon cooling to room temperature, the reaction was concentrated in vacuo and the residue obtained was partitioned between water (2 mL) & a mixture of CHCl3/THF (4:1, 3 mL). Upon separation of the layers, the aqueous layer was extracted with additional CHCl3/THF (4:1, 3 mL), the combined layers were filtered and concentrated. The material obtained was dissolved in methylene chloride (0.75 mL) and to this solution was added trifluoroacetic acid (0.5 mL, 6.4 mmol). The resulting reaction mixture was stirred overnight at room temperature. The reaction was concentrated in vacuo, the residue re-dissolved in DMSO (1 mL), filtered and purified on Agilent A2 prep instrument mass triggered reverse phase chromatography (Waters Sunfire prep C18 10 mm 19×150 mm column). Concentration of fractions containing desired product afforded product (0.0061 g, 26% yield). LCMS: (FA) ES+ 390.

1. additionInto a microwave vial containing
2. customThe vial was flushed with nitrogen gas
3. temperatureUpon cooling to room temperature
4. concentrationthe reaction was concentrated in vacuo
5. customthe residue obtained
6. customwas partitioned between water (2 mL)
7. additiona mixture of CHCl3/THF (4:1, 3 mL)
8. customUpon separation of the layers
9. extractionthe aqueous layer was extracted with additional CHCl3/THF (4:1, 3 mL)
10. filtrationthe combined layers were filtered
11. concentrationconcentrated
12. customThe material obtained
13. customThe resulting reaction mixture
14. concentrationThe reaction was concentrated in vacuo
15. dissolutionthe residue re-dissolved in DMSO (1 mL)
16. filtrationfiltered
17. custompurified on Agilent A2
18. additionConcentration of fractions containing desired product