Barbituric Acid → (2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-1,2,4-triazol-5-yl)-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(1-methyl-1H-1,2,4-triazol-5-yl)benzo[d]isoxazole-5-carbaldehyde (Intermediate 537, 124 mg, 0.35 mmol) and pyrimidine-2,4,6(1H,3H,5H)-trione (44.2 mg, 0.35 mmol) in methanol (3 ml) was heated at 150° C. for 1 hour in a microwave reactor. Solvent was removed and the residue was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% TFA). The solid was taken up in 9:1 CH2Cl2— MeOH and washed with NaHCO3 and brine. The aqueous layers were repeatedly extracted with additional 9:1 CH2Cl2-MeOH with each extract being washed with brine. The combined organic layers were dried (MgSO4) and concentrated and the residue was dissolved in THF. After removal of solvent, the solid residue was dried in vacuo at 50° C. overnight to afford desired product.

Provenance & Evidence