反应详情

温度

120 °C

A microwaveable vial was charged with 6-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (for a preparation see Intermediate 6) (74 mg, 0.192 mmol), 1-(2-methoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (CAS No. 847818-71-7 available from Milestone PharmTech USA Inc.) (63 mg, 0.250 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (21 mg, 0.029 mmol), potassium carbonate (56 mg, 0.405 mmol), water (0.5 ml), and 1,4-dioxane (1.5 ml). The vial was sealed and heated at 120° C. for 30 min (microwave). The reaction solution was diluted with water (10 ml), extracted with ethyl acetate (3×15 ml). The organics were combined, dried (hydrophobic frit). The solvent was evaporated in vacuo. The residue was dissolved in methanol/DMSO (1:1, 1 ml) and purified by MDAP (TFA). The solvent was evaporated under a stream of nitrogen, the residue was redissolved in methanol and filtered through an aminopropyl SPE (2 g). The solvent was evaporated in vacuo, to give 6-(((2S,4R)-1-acetyl-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (40 mg) as a white solid.

1. customThe vial was sealed
2. extractionextracted with ethyl acetate (3×15 ml)
3. customdried (hydrophobic frit)
4. customThe solvent was evaporated in vacuo
5. dissolutionThe residue was dissolved in methanol/DMSO (1:1, 1 ml)
6. custompurified by MDAP (TFA)
7. customThe solvent was evaporated under a stream of nitrogen
8. dissolutionthe residue was redissolved in methanol
9. filtrationfiltered through an aminopropyl SPE (2 g)
10. customThe solvent was evaporated in vacuo