Thioglycolic Acid → 2-[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]-2H-[1,2,4]triazine-3,5-dione

HRID 2199164Notes

Reaction equation

HRID 2199164 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[S:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[NH:11][N:10]=1.C(O)(=O)CS.C(=O)(O)[O-].[Na+]>O.[OH-].[Na+]>[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[S:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:16])[CH3:17])[C:12](=[O:18])[NH:11][N:10]=1

Participants

6

Reactant 3

HCID 1133Thioglycolic AcidHCID 516892Sodium BicarbonateHCID 598344482-[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid

Product 1

HCID 598344802-[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]-2H-[1,2,4]triazine-3,5-dioneYield 37.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
170 °C

Procedure

A mixture of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid (89) (1.0 g, 2.13 mmol) and thioglycolic acid (21.3 mL, 2.13 mmol) were heated at 170° C. for 3.5 h. At this time, the reaction was cooled to 25° C. and diluted with water (500 mL). The aqueous layer was brought to pH=4 by the addition of a saturated aqueous sodium bicarbonate solution. The solids that precipitated were collected by filtration, washed consecutively with water, petroleum ether, a pH=5 buffer and water. The solids were air-dried under house vacuum for 15 min and then dried under vacuum to give a light brown solid. This solid was dissolved in a 1N aqueous sodium hydroxide solution (100 mL) and extracted with ethyl acetate (1×120 mL). The aqueous layer was neutralized by the addition of a 1N aqueous hydrochloric acid solution (15 mL). The resulting solids were collected by filtration, washed with water (200 mL) and petroleum ether (100 mL), air-dried under house vacuum and then dried under vacuum to afford 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]-2H-[1,2,4]triazine-3,5-dione (90) (338 mg, 37%) as tan solid; ES(+)-HRMS m/e calcd for C16H13Cl2N5O3S (M+H)+ 426.0189, found 426.0189. Exact Mass=425.0116; Molecular weight=426.28

Workup

  1. temperatureAt this time, the reaction was cooled to 25° C.
  2. customThe solids that precipitated
  3. filtrationwere collected by filtration
  4. washwashed consecutively with water, petroleum ether
  5. customThe solids were air-dried under house vacuum for 15 min
  6. customdried under vacuum
  7. customto give a light brown solid
  8. extractionextracted with ethyl acetate (1×120 mL)
  9. additionThe aqueous layer was neutralized by the addition of a 1N aqueous hydrochloric acid solution (15 mL)
  10. filtrationThe resulting solids were collected by filtration
  11. washwashed with water (200 mL) and petroleum ether (100 mL)
  12. customair-dried under house vacuum
  13. customdried under vacuum

Sources & evidence

ORD record
ord-70127d0842804315a9166e9054002c8a
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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