Reacción #332738

Ecuación de reacción

6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(thiazol-2-yl)benzo[d]isoxazole-5-carbaldehyde

Intermediate 430

6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(thiazol-2-yl)benzo[d]isoxazole-5-carbaldehyde

pyrimidine-2,4,6(1H,3H,5H)-trione

→

title compound

Rendimiento 71.6%

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(thiazol-2-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

Rendimiento 71.6%

Disolventes

ethanol

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroSolvent removed
2. 2
   OtroLCMS of crude reaction
3. 3
   workup.ADDITION9:1 mixture of two diastereomeric products
4. 4
   OtroThe major product was purified by reverse phase preparative HPLC

Procedimiento

A mixture of 6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(thiazol-2-yl)benzo[d]isoxazole-5-carbaldehyde (Intermediate 430, 1.414 g, 3.91 mmol) and pyrimidine-2,4,6(1H,3H,5H)-trione (0.501 g, 3.91 mmol) in ethanol (200 ml) was heated at 90° C. for 5 days. Solvent removed. LCMS of crude reaction indicates 9:1 mixture of two diastereomeric products. The major product was purified by reverse phase preparative HPLC to give the title compound (1.320 g, 71.6%).

Fuente