Cesium carbonate → 3-(4,5-dibromo-2-methyl-2H-pyrazol-3-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432696Notes

Reaction equation

HRID 1432696 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:17][C:18]1[C:22]([Br:23])=[C:21](Br)[N:20]([CH3:25])[N:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Br:23][C:22]1[C:18]([Br:17])=[N:19][N:20]([CH3:25])[C:21]=1[C:13]1[N:8]2[N:9]=[C:10]([CH3:12])[CH:11]=[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]2=[N:15][C:14]=1[CH3:16]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 133340543,4,5-Tribromo-1-methyl-1H-pyrazoleHCID 688412672,6-Dimethyl-8-(pentan-3-yl)imidazo[1,2-b]pyridazine

Product 1

HCID 579329713-(4,5-dibromo-2-methyl-2H-pyrazol-3-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

8-(1-Ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (300 mg, 1.4 mmol), 3,4,5-tribromo-1-methyl-1H-pyrazole (700 mg, 2.1 mmol) and cesium carbonate (900 mg, 2.8 mmol) are stirred in DMF (5 ml) and degassed by bubbling a stream of nitrogen through the mixture. PdCl2(PPh3)2 (14 mg) is added and the mixture heated to 130° C. overnight. The mixture is added to water and extracted twice with EtOAc. The combined organic extracts are washed with brine, dried over Na2SO4, filtered and concentrated. The crude product is purified by chromatography using a hexane-ethyl acetate gradient (100% hexane to 20% ethyl acetate in hexane) to elute the title product (204 mg, 32% yield). ES-MS (m/z): calc'd for C17H21Br2N5: 455.2. found 455.9 (M+H)+. 1H NMR (400 mHz, CDCl3): δ 6.75 (s, 1H), 3.72 (s, 3H), 3.33 (m, 1H), 2.51 (s, 3H), 2.45 (s, 3H), 1.84 (m, 4H), 0.88 (t, 6H).

Workup

  1. customdegassed
  2. customby bubbling a stream of nitrogen through the mixture
  3. additionPdCl2(PPh3)2 (14 mg) is added
  4. additionThe mixture is added to water
  5. extractionextracted twice with EtOAc
  6. washThe combined organic extracts are washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product is purified by chromatography

Sources & evidence

ORD record
ord-006bcd88790c4f5797b2c9ff0f673125
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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