Cesium carbonate → 3-(1-Methyl-3-phenyl-1H-pyrazol-4-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432719Notes

Reaction equation

HRID 1432719 reaction equation
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([CH:13]=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].Br[C:18]1[C:19]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:20][N:21]([CH3:23])[CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH3:23][N:21]1[CH:22]=[C:18]([C:13]2[N:8]3[N:9]=[C:10]([CH3:12])[CH:11]=[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]3=[N:15][C:14]=2[CH3:16])[C:19]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[N:20]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 136924404-Bromo-1-methyl-3-phenyl-1H-pyrazoleHCID 688412672,6-Dimethyl-8-(pentan-3-yl)imidazo[1,2-b]pyridazine

Product 1

HCID 579329403-(1-Methyl-3-phenyl-1H-pyrazol-4-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 6.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

8-(1-Ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (160 mg, 0.73 mmol), 4-bromo-1-methyl-3-phenyl-1H-pyrazole (250 mg, 1.1 mmol) and cesium carbonate (490 mg, 1.50 mmol) are stirred in DMF (5 ml) and degassed by bubbling a stream of nitrogen through the mixture. PdCl2(PPh3)2 (15 mg) is added and the mixture is heated to 130° C. overnight. The mixture is added to water and extracted twice with ethyl acetate. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude product is purified by chromatography using a hexane-ethyl acetate gradient (100% hexane to 50% ethyl acetate in hexane) to elute the title compound (17.5 mg, 4% yield). ES-MS (m/z): calc'd for C23H27N5: 373.5; found 374.2 (M+H)+. 1H NMR (400 mHz, CDCl3): δ 7.68 (s, 1H), 7.37 (m, 2H), 7.20 (m, 3H), 6.59 (s, 1H), 4.04 (s, 3H), 3.36 (m, 1H), 2.38 (s, 3H), 2.15 (s, 3H), 1.82 (m, 4H), 0.86 (t, 6H).

Workup

  1. customdegassed
  2. customby bubbling a stream of nitrogen through the mixture
  3. additionPdCl2(PPh3)2 (15 mg) is added
  4. additionThe mixture is added to water
  5. extractionextracted twice with ethyl acetate
  6. dry with materialThe combined organic extracts are dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is purified by chromatography

Sources & evidence

ORD record
ord-8ad67f64f2c24d618c6a2e489c1b05a3
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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