反应详情

温度

120 °C

To a microwave vial was added (5R)-7-methyl-2-(6-methyl-2-pyridyl)-1,7-diazaspiro[4.4]non-1-en-6-one (which may be prepared as described in Description 32) (100 mg, 0.4100 mmol), 4,4′-di-tert-butyl-2,2′-bipyridyl (11.03 mg, 0.0400 mmol), bis(pinocolato)-diboron (156.55 mg, 0.6200 mmol), and (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (13.62 mg, 0.0200 mmol). The microwave vial was sealed and evacuated and filled with nitrogen three times. 1,2-dimethoxyethane (2 mL) was then added and the reaction was heated in the microwave at 120° C. for 10 minutes. The vessel was cooled and a solution of sodium carbonate (217.81 mg, 2.06 mmol) in water (1 mL) was added, followed by 1-bromo-4-fluorobenzene (0.06 mL, 0.5100 mmol), and finally 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride-dichloromethane complex (16.82 mg, 0.0200 mmol). The reaction was then resealed, and heated in a microwave at 130° C. for 10 minutes. The cooled reaction mixture was partitioned between EtOAc (15 mL) and water (10 mL). The organics were separated, washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was loaded onto silica (10 g SNAP column), and this was eluted with MeOH:EtOAc, 0% to 16%. Fractions containing desired product were combined and concentrated in vacuo to give (5R)-2-[4-(4-fluorophenyl)-6-methyl-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]non-1-en-6-one (D33R) (65 mg, 0.1927 mmol, 46.9% yield) as a colourless oil;

1. customThe microwave vial was sealed
2. customevacuated
3. additionfilled with nitrogen three times
4. addition1,2-dimethoxyethane (2 mL) was then added
5. temperatureThe vessel was cooled
6. temperatureheated in a microwave at 130° C. for 10 minutes
7. customThe cooled reaction mixture
8. customwas partitioned between EtOAc (15 mL) and water (10 mL)
9. customThe organics were separated
10. washwashed with brine
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. washthis was eluted with MeOH
15. additionFractions containing desired product
16. concentrationconcentrated in vacuo