Cesium carbonate → 5-chloro-3-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)pyridazine

HRID 1498788Notes

Reaction equation

HRID 1498788 reaction equation
Cl[C:2]1[N:3]=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:15][C:16]1[N:20]=[C:19]([CH3:21])[NH:18][N:17]=1>O1CCCC1>[Cl:8][C:6]1[CH:7]=[C:2]([N:17]2[C:16]([CH3:15])=[N:20][C:19]([CH3:21])=[N:18]2)[N:3]=[N:4][CH:5]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 1390011H-1,2,4-Triazole, 3,5-dimethyl-HCID 199596873,5-Dichloropyridazine

Product 1

HCID 867320485-chloro-3-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)pyridazine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring solution of 3,5-dichloropyridazine (23-1, 5.00 g, 33.5 mmol, 1.0 eq.) in tetrahydrofuran (125 ml) at 0° C. was added cesium carbonate (17.7 g, 50.3 mmol, 1.5 eq.), followed by 3,5-dimethyl-1H-1,2,4-triazole (3.25 g, 33.5 mmol, 1.0 eq.) in tetrahydrofuran (125 mL) dropwise. The resulting reaction mixture was stirred for 1 hour at the same temperature and then warmed to room temperature and stirred for another 3 hours, then heated to 60° C. and stirred for 6 hours. The solvent was removed under reduced pressure and the residue was diluted with water (200 mL) and extracted with DCM (3×80 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (70% ethyl acetate in hexanes) to afford 5-chloro-3-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)pyridazine (23-2) as a white solid. 1H NMR (300 MHz, CDCl3) δ 9.11 (d, 1H, J=2.1 Hz), 8.20 (d, 1H, J=2.1 Hz), 2.96 (s, 3H), 2.43 (s, 3H).

Workup

  1. customThe resulting reaction mixture
  2. stirringstirred for another 3 hours
  3. temperatureheated to 60° C.
  4. stirringstirred for 6 hours
  5. customThe solvent was removed under reduced pressure
  6. additionthe residue was diluted with water (200 mL)
  7. extractionextracted with DCM (3×80 mL)
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel column chromatography (70% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-dd407094c7ff4e939180a769b123f4f5
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

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