Cesium carbonate → 8-(1-Ethyl-propyl)-2,6-dimethyl-3-{2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl}imidazo[1,2-b]pyridazine

HRID 226024Notes

Reaction equation

HRID 226024 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH3:10])=[N:6][N:5]2[CH:11]=1.[CH2:12]([CH:14]([C:17]1[C:18]2[N:19]([C:24](I)=[C:25]([CH3:27])[N:26]=2)[N:20]=[C:21]([CH3:23])[CH:22]=1)[CH2:15][CH3:16])[CH3:13].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:12]([CH:14]([C:17]1[C:18]2[N:19]([C:24]([C:11]3[N:5]4[N:6]=[C:7]([CH3:10])[CH:8]=[CH:9][C:4]4=[N:3][C:2]=3[CH3:1])=[C:25]([CH3:27])[N:26]=2)[N:20]=[C:21]([CH3:23])[CH:22]=1)[CH2:15][CH3:16])[CH3:13]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 218176672,6-Dimethylimidazo[1,2-b]pyridazineHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine

Product 1

HCID 688572858-(1-Ethyl-propyl)-2,6-dimethyl-3-{2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl}imidazo[1,2-b]pyridazineYield 34.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

A mixture containing 2,6-dimethyl-imidazo[1,2-b]pyridazine (0.44 g, 2.99 mmol), 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (1.03 g, 2.99 mmol), Pd(OAc)2 (34 mg, 0.15 mmol), PPh3 (79 mg, 0.299 mmol), Cs2CO3 (1.95 g, 6.0 mmol) in DMF (50 mL) is stirred under N2 at 130-140° C. overnight. The reaction mixture is cooled, diluted with EtOAc (300 mL), washed with H2O (3×100 mL); dried (Na2SO4); filtered and concentrated. Purification of the resulting crude material by chromatography yields the title compound (0.37 g, 1.02 mmol, 34%). 1H NMR (CDCl3): δ 0.92 (t, J=7.1 Hz, 6H), 1.80-1.95 (m, 4H), 2.43 (s, 3H), 2.44 (s, 3H), 2.46 (s, 3H), 2.50 (s, 3H), 3.35-3.43 (m, 1H), 6.69 (s, 1H), 6.92 (d, J=9.2 Hz, 1H), 7.82 (d, J=1H) ppm. ES-MS (m/z): calcd for C21H26N6 (M+H)+: 363.5. found: 363.3.

Workup

  1. temperatureThe reaction mixture is cooled
  2. washwashed with H2O (3×100 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the resulting crude material by chromatography

Sources & evidence

ORD record
ord-e8f0b6c82a104f1aa1a6458fdd7d3154
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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