Thioglycolic Acid → HCID 15981238, compound

HRID 2199120Notes

Reaction equation

HRID 2199120 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:20]2[C:25](=[O:26])[NH:24][C:23](=[O:27])[C:22](C(O)=O)=[N:21]2)[CH:5]=[C:6]([Cl:19])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[NH:11][N:10]=1.SCC(O)=O>O>[Cl:1][C:2]1[CH:3]=[C:4]([N:20]2[C:25](=[O:26])[NH:24][C:23](=[O:27])[CH:22]=[N:21]2)[CH:5]=[C:6]([Cl:19])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[NH:11][N:10]=1

Participants

4

Reactant 2

HCID 1133Thioglycolic AcidHCID 59834482920509-35-9

Product 1

HCID 15981238HCID 15981238, compoundYield 23.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
170 °C

Procedure

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

Workup

  1. temperatureAt this time, the reaction mixture was cooled to room temperature
  2. extractionwas extracted with ethyl acetate (100 mL)
  3. customThe organic layer was separated
  4. washwashed with a saturated aqueous sodium bicarbonate solution (2×100 mL)
  5. dry with materiala saturated aqueous sodium chloride solution (100 mL), dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. dissolutionThe resulting solid was dissolved in methylene chloride
  9. customwas purified by flash chromatography (Biotage 40S)
  10. washeluted with 100% ethyl acetate
  11. washto elute the impurity
  12. washto elute the desired product
  13. customThe desired fractions were collected
  14. concentrationconcentrated under vacuum
  15. filtrationfiltered
  16. washrinsed with petroleum ether
  17. customThe solids were dried in a vacuum oven at 80° C.

Sources & evidence

ORD record
ord-e8a8c86ab3b241cc94d09579bfefd9fe
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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