تفاعل #2286302

معادلة التفاعل

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

المردود 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

المردود 23.7%

المذيبات

water

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةAt this time, the reaction mixture was cooled to room temperature
2. 2
   استخلاصwas extracted with ethyl acetate (100 mL)
3. 3
   أخرىThe organic layer was separated
4. 4
   غسيلwashed with a saturated aqueous sodium bicarbonate solution (2×100 mL)
5. 5
   تجفيفa saturated aqueous sodium chloride solution (100 mL), dried with magnesium sulfate
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated under vacuum
8. 8
   workup.DISSOLUTIONThe resulting solid was dissolved in methylene chloride
9. 9
   أخرىwas purified by flash chromatography (Biotage 40S)
10. 10
    غسيلeluted with 100% ethyl acetate
11. 11
    غسيلto elute the impurity
12. 12
    غسيلto elute the desired product
13. 13
    أخرىThe desired fractions were collected
14. 14
    تركيزconcentrated under vacuum
15. 15
    ترشيحfiltered
16. 16
    غسيلrinsed with petroleum ether
17. 17
    أخرىThe solids were dried in a vacuum oven at 80° C.

الإجراء التجريبي

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

المصدر