Water → 6-(2-Methyl-2 H-1,2,4-triazol-3-ylmethoxy)-3-phenyl-7-(pyrrolidin-1-vl)-1,2,4-triazolo[4,3-b]pyridazine

HRID 47230Notes

Reaction equation

HRID 47230 reaction equation
[CH3:1][N:2]1[C:6]([CH2:7][OH:8])=[N:5][CH:4]=[N:3]1.[H-].[Na+].Cl[C:12]1[C:13]([N:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)=[CH:14][C:15]2[N:16]([C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:19][N:20]=2)[N:17]=1.O>CN(C=O)C>[CH3:1][N:2]1[C:6]([CH2:7][O:8][C:12]2[C:13]([N:27]3[CH2:28][CH2:29][CH2:30][CH2:31]3)=[CH:14][C:15]3[N:16]([C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:19][N:20]=3)[N:17]=2)=[N:5][CH:4]=[N:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 11073377(1-methyl-1H-1,2,4-triazol-5-yl)methanolHCID 227441646-Chloro-3-phenyl-7-(1-pyrrolidinyl)-1,2,4-triazolo[4,3-b]pyridazine

Product 1

HCID 98859896-(2-Methyl-2 H-1,2,4-triazol-3-ylmethoxy)-3-phenyl-7-(pyrrolidin-1-vl)-1,2,4-triazolo[4,3-b]pyridazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (2-methyl-2H-1,2,4-triazol-3-yl)methanol (2.5 g, 0.022 mol; EP-A-421210) in DMF (200 ml) was added a 60% suspension of sodium hydride in mineral oil (1.2 g, 0.031 mol), and the resultant slurry was stirred at room temperature under nitrogen for 1 h. 6-Chloro-3-phenyl-7-(pyrrolidin-1-yl)-1,2,4-triazolo[4,3-b]pyridazine (6.0 g, 0.020 mol) was added, and the mixture was stirred as before for 30 min. Water (600 ml) was added, precipitating a solid. This was filtered off, then washed with water and diethyl ether. The crude product was dissolved in a mixture of ethanol (50 ml) and dichloromethane (110 ml), and then the chlorinated solvent was boiled off. The resultant solution was cooled to 4° C. precipitating the title compound as a white solid (6.3 g, 83%). 1H NMR (400 MHz, CDCl3) δ1.97 (4H, m), 3.47 (4H, m), 3.97 (3H, s), 5.59 (2H, s), 6.72 (1H, s), 7.48 (3H, m), 7.95 (1H, s), 8.28 (2H, m); MS (ES+) m/e 377[MH]+.

Workup

  1. stirringthe mixture was stirred as before for 30 min
  2. customprecipitating a solid
  3. filtrationThis was filtered off
  4. washwashed with water and diethyl ether
  5. dissolutionThe crude product was dissolved in a mixture of ethanol (50 ml) and dichloromethane (110 ml)
  6. temperatureThe resultant solution was cooled to 4° C.
  7. customprecipitating the title compound as a white solid (6.3 g, 83%)

Sources & evidence

ORD record
ord-a92ef95f6fb443cb8a5a80624dc60106
Source dataset
uspto-grants-2004_03
Patent number
US06699859B1

Reaction notes

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