1-Methylimidazole → 8-(1-ethyl-propyl)-2,6-dimethyl-3-[3-methyl-5-(1-methyl-1H-imidazol-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazine

HRID 1432575Notes

Reaction equation

HRID 1432575 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:11]3[N:12]=[C:13]([CH3:21])[CH:14]=[C:15]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:10]3=[N:9][C:8]=2[CH3:22])=[C:4]([CH3:23])[CH:3]=1.[CH3:24][N:25]1[CH:29]=[CH:28][N:27]=[CH:26]1.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]>[CH2:17]([CH:16]([C:15]1[C:10]2[N:11]([C:7]([C:5]3[S:6][C:2]([C:26]4[N:25]([CH3:24])[CH:29]=[CH:28][N:27]=4)=[CH:3][C:4]=3[CH3:23])=[C:8]([CH3:22])[N:9]=2)[N:12]=[C:13]([CH3:21])[CH:14]=1)[CH2:19][CH3:20])[CH3:18]

Participants

8

Reactant 4

HCID 13901-MethylimidazoleHCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 579329433-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

Product 1

HCID 579329548-(1-ethyl-propyl)-2,6-dimethyl-3-[3-methyl-5-(1-methyl-1H-imidazol-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazineYield 51%

Reagents, catalysts & solvents 3

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

Procedure

3-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo-[1,2-b]pyridazine (0.98 g, 2.51 mmol) and 1-methyl-1H-imidazole (0.2 mL), 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 (0.51 g, 1.29 mmol, 51%). 1H NMR (CDCl3): δ 0.89 (t, J=7.5 Hz, 6H), 1.77-1.92 (m, 4H), 2.17 (s, 3H), 2.51 (s, 3H), 2.54 (s, 3H), 3.30-3.40 (m, 1H), 3.81 (s, 3H), 6.69 (s, 1H), 7.02 (s, 1H), 7.24 (s, 1H), 7.52 (s, 1H). ES-MS (m/z): calcd for C22H27N5S (M+H)+: 394.6; found: 394.3.

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-ce0c3d98b9b24ef799fdcbd9e845881d
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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