Nicotinic acid, hydrazide → Quinoxaline

HRID 842660Notes

Reaction equation

HRID 842660 reaction equation
Cl[C:2]1[C:3](NC(=S)COC)=[C:4]2[C:9](=[CH:10][C:11]=1Cl)[N:8]=[C:7](OC)[C:6](OC)=[N:5]2.C(NN)(=O)C1C=CC=NC=1>[Hg]=O.O1CCOCC1>[N:5]1[C:4]2[C:9](=[CH:10][CH:11]=[CH:2][CH:3]=2)[N:8]=[CH:7][CH:6]=1

Participants

5

Reactant 2

HCID 11112Nicotinic acid, hydrazideHCID 18726777HCID 18726777, compound

Product 1

HCID 7045QuinoxalineYield 127.5%

Reagents, catalysts & solvents 2

HCID 30856Mercuric oxideCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6,7-dichloro-2,3-dimethoxy-5-methoxythioacetamidoquinoxaline (25.3 g, 69.9 mmol), nicotinic acid hydrazide (19.3 g, 140.8 mmol), mercury(II) oxide (15.1 g, 69.7 mmol) and 1,4-dioxane (600 mL) was heated under reflux for 18 hours. After cooling, the mixture was filtered through ARBOCEL (trade mark) filter aid and the residue washed with dichloromethane. The filtrate was concentrated under reduced pressure to afford a light brown solid which was partitioned between ethyl acetate and 2M aqueous hydrochloric acid solution. The layers were separated and the aqueous layer was extracted with dichloromethane (2×500 mL, 4×100 mL). The combined dichloromethane extracts were dried (MgSO4) and concentrated under reduced pressure. The residue was crystallised from ethyl acetate/methanol to give (±)-6,7-dichloro-2,3-dimethoxy-5-[3-methoxymethyl-5-(3-pyridyl)-4H-1,2,4-triazol-4-yl)]quinoxaline (11.6 g, 37%) as a pale yellow solid, mp 189-191° C.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 18 hours
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered through ARBOCEL (trade mark)
  5. filtrationfilter aid
  6. washthe residue washed with dichloromethane
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customto afford a light brown solid which
  9. customwas partitioned between ethyl acetate and 2M aqueous hydrochloric acid solution
  10. customThe layers were separated
  11. extractionthe aqueous layer was extracted with dichloromethane (2×500 mL, 4×100 mL)
  12. dry with materialThe combined dichloromethane extracts were dried (MgSO4)
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was crystallised from ethyl acetate/methanol

Sources & evidence

ORD record
ord-08995db5a3e242ce844b5833df02f266
Source dataset
uspto-grants-2002_04
Patent number
US06376490B1

Reaction notes

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