Reaktion #2286302

Reaktionsgleichung

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

Ausbeute 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

Ausbeute 23.7%

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAt this time, the reaction mixture was cooled to room temperature
2. 2
   Extraktionwas extracted with ethyl acetate (100 mL)
3. 3
   SonstigeThe organic layer was separated
4. 4
   Waschenwashed with a saturated aqueous sodium bicarbonate solution (2×100 mL)
5. 5
   Trocknena saturated aqueous sodium chloride solution (100 mL), dried with magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated under vacuum
8. 8
   workup.DISSOLUTIONThe resulting solid was dissolved in methylene chloride
9. 9
   Sonstigewas purified by flash chromatography (Biotage 40S)
10. 10
    Wascheneluted with 100% ethyl acetate
11. 11
    Waschento elute the impurity
12. 12
    Waschento elute the desired product
13. 13
    SonstigeThe desired fractions were collected
14. 14
    Einengenconcentrated under vacuum
15. 15
    Filtrationfiltered
16. 16
    Waschenrinsed with petroleum ether
17. 17
    SonstigeThe solids were dried in a vacuum oven at 80° C.

Vorschrift

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

Quelle