1H-1,2,4-Triazole → 7-([1,2,4]Triazol-1-ylmethyl)imidazo[1,2-alpha]pyrimidine

HRID 1796101Notes

Reaction equation

HRID 1796101 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[H-].[Na+].Cl.Cl[CH2:10][C:11]1[CH:16]=[CH:15][N:14]2[CH:17]=[CH:18][N:19]=[C:13]2[N:12]=1.C(=O)([O-])[O-].[K+].[K+].[Na].N1C=CN=N1>CN(C)C=O>[N:1]1([CH2:10][C:11]2[CH:16]=[CH:15][N:14]3[CH:17]=[CH:18][N:19]=[C:13]3[N:12]=2)[CH:5]=[N:4][CH:3]=[N:2]1

Participants

7

Reactant 5

HCID 92571H-1,2,4-TriazoleHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 695607647-Chloromethylimidazo[1,2-alpha]pyrimidine hydrochloride2×HCID 178507080HCID 178507080, compound

Product 1

HCID 695603727-([1,2,4]Triazol-1-ylmethyl)imidazo[1,2-alpha]pyrimidineYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a solution of 1H-[1,2,4]triazole (2.2 g, 31.9 mmol) in anhydrous N,N-dimethylformamide (20 ml) under a nitrogen atmosphere was added sodium hydride (1.18 g, 29.4 mmol, 60% dispersion in oil) with caution in a portionwise manner. This mixture was then stirred for 20 min at room temperature. To a separate solution of 7-chloromethylimidazo[1,2-α]pyrimidine hydrochloride (5.0 g, 24.5 mmol), also dissolved in N,N-dimethylformamide (50 ml) under nitrogen, was added potassium carbonate (6.76 g, 49.0 mmol) and the mixture stirred for 5 min at room temperature. To the 7-chloromethylimidazo[1,2-α]pyrimidine solution was added the triazole sodium salt as a solution in N,N-dimethylformamide and the mixture stirred at room temperature for 16 h. Solvent was removed under reduced pressure and the resulting residue purified by flash column chromatography on silica eluting with dichloromethene, methanol and aqueous ammonia solution (33%) in the ratios 90:5:0.5 respectively to give 7-([1,2,4]triazol-1-ylmethyl)imidazo[1,2-α]pyrimidine (3.38 g, 69%) as a tan solid: δH (360 Mz, d6-DMSO) 5.63 (2H, s), 6.90 (1H, d, J 7), 7.71 (1H, d, J 1.3), 7.91 (1H, d, J 1.4), 8.04 (1H, s), 8.73 (1H, s), 8.97 (1H, d, J 7); m/z (ES+) 201 (M++H).

Workup

  1. stirringthe mixture stirred for 5 min at room temperature
  2. stirringthe mixture stirred at room temperature for 16 h
  3. customSolvent was removed under reduced pressure
  4. customthe resulting residue purified by flash column chromatography on silica eluting with dichloromethene, methanol and aqueous ammonia solution (33%) in the ratios 90:5:0.5 respectively

Sources & evidence

ORD record
ord-ebfe4b700d62415c871a6f49e7011064
Source dataset
uspto-grants-2006_04
Patent number
US07030128B2

Reaction notes

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