Реакция #2286302

Уравнение реакции

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

Выход 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

Выход 23.7%

Растворители

water

Условия реакции

Обработка

1. 1
   ТемператураAt this time, the reaction mixture was cooled to room temperature
2. 2
   Экстракцияwas extracted with ethyl acetate (100 mL)
3. 3
   ДругоеThe organic layer was separated
4. 4
   Промывкаwashed with a saturated aqueous sodium bicarbonate solution (2×100 mL)
5. 5
   Сушкаa saturated aqueous sodium chloride solution (100 mL), dried with magnesium sulfate
6. 6
   Фильтрацияfiltered
7. 7
   Концентрированиеconcentrated under vacuum
8. 8
   workup.DISSOLUTIONThe resulting solid was dissolved in methylene chloride
9. 9
   Другоеwas purified by flash chromatography (Biotage 40S)
10. 10
    Промывкаeluted with 100% ethyl acetate
11. 11
    Промывкаto elute the impurity
12. 12
    Промывкаto elute the desired product
13. 13
    ДругоеThe desired fractions were collected
14. 14
    Концентрированиеconcentrated under vacuum
15. 15
    Фильтрацияfiltered
16. 16
    Промывкаrinsed with petroleum ether
17. 17
    ДругоеThe solids were dried in a vacuum oven at 80° C.

Методика

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

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