Reacción #332734

ord-8077009b7f4647a4849327bc3813032d

Ecuación de reacción

C[C@@H]1CN(c2c(C=O)cc3c(-n4cncn4)noc3c2F)C[C@@H](C)O1
6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(1H-1,2,4-triazol-1-yl)benzo[d]isoxazole-5-carbaldehyde
C[C@@H]1CN(c2c(C=O)cc3c(-n4cncn4)noc3c2F)C[C@@H](C)O1
Intermediate 574
C[C@@H]1CN(c2c(C=O)cc3c(-n4cncn4)noc3c2F)C[C@@H](C)O1
6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(1H-1,2,4-triazol-1-yl)benzo[d]isoxazole-5-carbaldehyde
O=C1CC(=O)NC(=O)N1
pyrimidine-2,4,6(1H,3H,5H)-trione
C[C@@H]1CN2c3c(cc4c(-n5cncn5)noc4c3F)CC3(C(=O)NC(=O)NC3=O)[C@H]2[C@H](C)O1
product
Rendimiento 43.9%
C[C@@H]1CN2c3c(cc4c(-n5cncn5)noc4c3F)CC3(C(=O)NC(=O)NC3=O)[C@H]2[C@H](C)O1
(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(1H-1,2,4-triazol-1-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 43.9%

Disolventes

Condiciones de reacción

Temperatura
150°CELSIUS
Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    OtroThe reaction mixture was purified by Super Critical Fluid chromatography on a Chiralpac IC column with a 35% MeOH, 65% CO2 mobile phase

Procedimiento

A mixture of 6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(1H-1,2,4-triazol-1-yl)benzo[d]isoxazole-5-carbaldehyde (Intermediate 574, 500 mg, 1.45 mmol) and pyrimidine-2,4,6(1H,3H,5H)-trione (185 mg, 1.45 mmol) in DMSO (6 ml) was heated at 150° C. for 2 hours in a microwave reactor. The reaction mixture was purified by Super Critical Fluid chromatography on a Chiralpac IC column with a 35% MeOH, 65% CO2 mobile phase to give 290 mg of product as a solid as the first eluting compound.

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US08658641B2uspto-grants-2014_02