反応 #2286302

反応方程式

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

収率 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

収率 23.7%

溶媒

water

反応条件

後処理

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

実験手順

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

出典