反应 #2286302

反应方程式

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

收率 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

收率 23.7%

溶剂

water

反应条件

后处理

1. 1
   温度At this time, the reaction mixture was cooled to room temperature
2. 2
   萃取was extracted with ethyl acetate (100 mL)
3. 3
   其他The organic layer was separated
4. 4
   洗涤washed with a saturated aqueous sodium bicarbonate solution (2×100 mL)
5. 5
   干燥a saturated aqueous sodium chloride solution (100 mL), dried with magnesium sulfate
6. 6
   过滤filtered
7. 7
   浓缩concentrated under vacuum
8. 8
   workup.DISSOLUTIONThe resulting solid was dissolved in methylene chloride
9. 9
   其他was purified by flash chromatography (Biotage 40S)
10. 10
    洗涤eluted with 100% ethyl acetate
11. 11
    洗涤to elute the impurity
12. 12
    洗涤to elute the desired product
13. 13
    其他The desired fractions were collected
14. 14
    浓缩concentrated under vacuum
15. 15
    过滤filtered
16. 16
    洗涤rinsed with petroleum ether
17. 17
    其他The solids were dried in a vacuum oven at 80° C.

实验过程

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

来源