Reacción #2286302

Ecuación de reacción

2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid

2-[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid

mercaptoacetic acid

→

2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-2H-[1,2,4]triazine-3,5-dione

Rendimiento 23.7%

2-[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-2H-[1,2,4]triazine-3,5-dione

Rendimiento 23.7%

Disolventes

water

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAt this time, the reaction mixture was cooled to room temperature
2. 2
   Extracciónwas extracted with ethyl acetate (100 mL)
3. 3
   OtroThe organic layer was separated
4. 4
   Lavadowashed with a saturated aqueous sodium bicarbonate solution (2×100 mL)
5. 5
   Secadoa saturated aqueous sodium chloride solution (100 mL), dried with magnesium sulfate
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated under vacuum
8. 8
   workup.DISSOLUTIONThe resulting solid was dissolved in methylene chloride
9. 9
   Otrowas purified by flash chromatography (Biotage 40S)
10. 10
    Lavadoeluted with 100% ethyl acetate
11. 11
    Lavadoto elute the impurity
12. 12
    Lavadoto elute the desired product
13. 13
    OtroThe desired fractions were collected
14. 14
    Concentraciónconcentrated under vacuum
15. 15
    Filtraciónfiltered
16. 16
    Lavadorinsed with petroleum ether
17. 17
    OtroThe solids were dried in a vacuum oven at 80° C.

Procedimiento

A mixture of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid (32) (102 mg, 0.22 mmol) and mercaptoacetic acid (2.2 mL) was heated to 170° C. for 1 h. At this time, the reaction mixture was cooled to room temperature and was diluted with water (120 mL) and was extracted with ethyl acetate (100 mL). The organic layer was separated and washed with a saturated aqueous sodium bicarbonate solution (2×100 mL) and a saturated aqueous sodium chloride solution (100 mL), dried with magnesium sulfate, filtered and concentrated under vacuum. The resulting solid was dissolved in methylene chloride and was purified by flash chromatography (Biotage 40S) using silica gel eluted with 100% ethyl acetate to elute the impurity followed by 0.2% glacial acetic acid in ethyl acetate to elute the desired product. The desired fractions were collected and concentrated under vacuum. The resulting solid was slurried in hot methanol (2 mL), filtered and rinsed with petroleum ether. The solids were dried in a vacuum oven at 80° C. to afford 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-2H-[1,2,4]triazine-3,5-dione (33) (21.4 mg, 23%) as a yellow solid; EI(+)-HRMS m/z calcd for C16H13Cl2N5O4 (M+) 410.0418, found 410.0419. Molecular Weight=410.2191; Exact Mass=409.0345

Fuente