Reacción #44232

Ecuación de reacción

2-Fluoro-4-methylphenylamine

rac-2,2-bis(diphenylphosphino)-1,1′-binaphthyl

cesium carbonate

4-chloro-1,3,8-trimethyl-1H,6H-pyrido[2,3-d]pyridazine-2,5-dione

→

desired product

4-(2-fluoro-4-methylphenylamino)-1,3,8-trimethyl-1H,6H-pyrido[2,3-d]pyridazine-2,5-dione

Disolventes

EtOAc

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.WAITAfter 24 hours
2. 2
   Temperaturathe reaction mixture is cooled to room temperature
3. 3
   FiltraciónThe resulting precipitate is filtered
4. 4
   Lavadowashed with EtOAc
5. 5
   workup.ADDITIONThe filtrate is diluted with EtOAc
6. 6
   Lavadowashed with water
7. 7
   LavadoThe combined organic layers are washed with brine
8. 8
   Secadodried (Na2SO4)
9. 9
   Concentraciónconcentrated
10. 10
    OtroPurification by flash column chromatography

Procedimiento

2-Fluoro-4-methylphenylamine (1.10 equivalents), palladium (II) acetate (0.10 equivalents), rac-2,2-bis(diphenylphosphino)-1,1′-binaphthyl (0.15 equivalents), and cesium carbonate (1.50 equivalents) are added to a solution of 4-chloro-1,3,8-trimethyl-1H,6H-pyrido[2,3-d]pyridazine-2,5-dione (1.00 equivalent) in toluene in a sealed vial. After stirring 10 minutes, the mixture is heated to 80° C. After 24 hours, the reaction mixture is cooled to room temperature and diluted with EtOAc. The resulting precipitate is filtered and washed with EtOAc. The filtrate is diluted with EtOAc and washed with water. The aqueous layer is reextracted with EtOAc. The combined organic layers are washed with brine, dried (Na2SO4) and concentrated. Purification by flash column chromatography gives the desired product.

Fuente