反应详情

温度

150 °C

To a solution of 7-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (Example 9) (27 mg, 0.05 mmol) in DMF (1.0 mL) was added 4-ethynyl-1H-pyrazole (6.9 mg, 0.07 mmol), bis(triphenylphosphine)-palladium (II) chloride (4.0 mg, 0.006 mmol), copper (I) iodide (2.0 mg, 0.01 mmol) and triethyl amine (0.06 mL, 0.43 mmol). In a sealed reaction vessel, the mixture was heated with microwave radiation at 150° C. for 20 minutes. After cooling to room temperature, removed solvent under reduced pressure to give an oily residue which was treated with methanol (5 mL) forming a suspension. Filtered solids and washed with ethyl acetate (10 mL) and DMF (1 mL). The combined filtrate was concentrated under reduced pressure and resulting brown oil was dissolved in ethyl acetate (50 mL), washed with 0.1N HCl (3×50 mL), saturated NaHCO3 aqueous solution (2×50 mL) and brine (1×50 mL). Dried over MgSO4, filtered and solvent removed under reduced pressure to give a light brown oil. Dissolved oil in hot ethyl acetate and silica gel (2.0 g) was added followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to isocratic elution using ethyl acetate:hexanes (50:50) followed by ethyl acetate:methanol (85:15) using a Biotage silica gel cartridge (8.0 g). The appropriate fractions were combined and concentrated under reduced pressure to give 5-methyl-7-[3-(1H-pyrazol-4-ylethynyl)phenyl]-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (0.0053 g) as a tan solid. MS m/z 482 (M+1).

1. customIn a sealed reaction vessel
2. temperatureAfter cooling to room temperature
3. customremoved solvent under reduced pressure
4. customto give an oily residue which
5. customforming a suspension
6. filtrationFiltered solids
7. washwashed with ethyl acetate (10 mL) and DMF (1 mL)
8. concentrationThe combined filtrate was concentrated under reduced pressure
9. customresulting brown oil
10. washwashed with 0.1N HCl (3×50 mL), saturated NaHCO3 aqueous solution (2×50 mL) and brine (1×50 mL)
11. dry with materialDried over MgSO4
12. filtrationfiltered
13. customsolvent removed under reduced pressure
14. customto give a light brown oil
15. additionsilica gel (2.0 g) was added
16. customfollowed by evaporation of the volatiles under reduced pressure
17. washsubjected to isocratic elution
18. concentrationconcentrated under reduced pressure