Isoniazid → Pyridine, 4-(4,5-dimethyl-4H-1,2,4-triazol-3-yl)-

HRID 273122Notes

Reaction equation

HRID 273122 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][NH:8][C:9](=O)[CH3:10].N1C(C)=CC=CC=1C.[C:20]([NH:28][NH2:29])(=O)[C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1>C(Cl)Cl>[CH3:7][N:8]1[C:9]([CH3:10])=[N:29][N:28]=[C:20]1[C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 3767IsoniazidHCID 6582N-MethylacetamideHCID 79372,6-LutidineHCID 65578Oxalyl chloride

Product 1

HCID 11600754Pyridine, 4-(4,5-dimethyl-4H-1,2,4-triazol-3-yl)-Yield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

860 μl (10 mmol) oxalyl chloride was slowly added to a solution of 731 mg (10 mmol) N-methyl-acetamide and 2.33 ml (20 mmol) 2,6-lutidine in 20 ml CH2Cl2 at 0° C. After 15 min 1.37 g (10 mmol) isonicotinic acid hydrazide was added in one portion. The resulting mixture was stirred at room temperature for 1 h and the neutralized with NaHCO3(sat). The phases were separated and the water phase was extracted with CH2Cl2. The combined organic phases were dried and concentrated. The residue was dissolve in 20 ml acetic acid and heated at 120° C. for 2 h. After cooling the solvent was removed. Flashchromatography (CH2Cl2/MeOH 10:1) afforded 765 mg (44%) of a grey/white solid. 1H NMR (CDCl3), d (ppm): 2.52 (s, 3 H) 3.66 (s, 3 H) 7.58 (d, 2 H) 8.76 (d, 2 H).

Workup

  1. customThe phases were separated
  2. extractionthe water phase was extracted with CH2Cl2
  3. customThe combined organic phases were dried
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolve in 20 ml acetic acid
  6. temperatureheated at 120° C. for 2 h
  7. temperatureAfter cooling the solvent
  8. customwas removed

Sources & evidence

ORD record
ord-bb9c9fceb48249e9bf2dbecec0d87f9d
Source dataset
uspto-grants-2008_11
Patent number
US07456200B2

Reaction notes

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