Potassium Carbonate → 6-(4-(2,4-Difluorophenyl)-1-methyl-1H-imidazol-5-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1930007Notes

Reaction equation

HRID 1930007 reaction equation
[CH:1]([C:4]1[N:8]2[N:9]=[C:10]([CH:13]=[N:14][CH3:15])[CH:11]=[CH:12][C:7]2=[N:6][N:5]=1)([CH3:3])[CH3:2].[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[CH:24]([N+:35]#[C-:36])S(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[C:24]1[N:35]=[CH:36][N:14]([CH3:15])[C:13]=1[C:10]1[CH:11]=[CH:12][C:7]2[N:8]([C:4]([CH:1]([CH3:2])[CH3:3])=[N:5][N:6]=2)[N:9]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 222368732,4-Difluoro-1-(isocyano(tosyl)methyl)benzeneHCID 57929895N-((3-Isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)methylene)methanamine

Product 1

HCID 579299656-(4-(2,4-Difluorophenyl)-1-methyl-1H-imidazol-5-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazineYield 23.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

N-((3-Isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)methylene)methanamine (0.154 g, 0.758 mmol; Preparation #AP.1.1) and 2,4-difluoro-1-(isocyano(tosyl)methyl)benzene (0.233 g, 0.758 mmol, J. W. Pharmlab) were added to a 25 mL flask in DMF (4 mL). To the mixture was added K2CO3 (0.105 g, 0.758 mmol) and the mixture was heated to about 60° C. for about 17 h. The solvent was removed in vacuo and the material was washed with saturated aqueous NaHCO3 (10 mL) and extracted with EtOAc (15 mL), dried over MgSO4, filtered and concentrated to dryness. The residue was purified by flash chromatography (using MeOH/DCM 0-5% gradient) and then triturated with Et2O and dried in a vacuum oven overnight to afford the title compound as an off-white solid (0.062 g, 23%): LC/MS (Table 1, Method g) Rt=2.03 min; MS m/z: 355.2 (M+1)+.

Workup

  1. customThe solvent was removed in vacuo
  2. washthe material was washed with saturated aqueous NaHCO3 (10 mL)
  3. extractionextracted with EtOAc (15 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by flash chromatography (using MeOH/DCM 0-5% gradient)
  8. customtriturated with Et2O
  9. customdried in a vacuum oven overnight

Sources & evidence

ORD record
ord-9c0fc50cd7054fcb9a446086e2f51bb1
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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