Cesium carbonate → 8-(1-Ethyl-propyl)-6-methyl-3-(3-methyl-thiophen-2-yl)-2-trifluoromethyl-imidazo[1,2-b]pyridazine

HRID 1432730Notes

Reaction equation

HRID 1432730 reaction equation
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].Br[C:21]1[S:22][CH:23]=[CH:24][C:25]=1[CH3:26].C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN1C(=O)CCC1>[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13]([C:21]3[S:22][CH:23]=[CH:24][C:25]=3[CH3:26])=[C:14]([C:16]([F:18])([F:19])[F:17])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 843142-Bromo-3-methylthiopheneHCID 688409078-(1-Ethyl-propyl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine

Product 1

HCID 579329478-(1-Ethyl-propyl)-6-methyl-3-(3-methyl-thiophen-2-yl)-2-trifluoromethyl-imidazo[1,2-b]pyridazineYield 8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

To a dry 10 ml round bottom flask with reflux condenser containing 8-(1-ethyl-propyl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine (300 mg, 1.11 mmol), 2-bromo-3-methyl-thiophene (216 mg, 1.22 mmol), and Cs2CO3 (760 mg, 2.33 mmol) is added NMP (1.7 ml). The mixture is degassed with bubbling N2 for 15 min and Pd2(dba)3 (50.8 mg, 0.055 mmol) and PPh3 (58.2 mg, 0.222 mmol) are added. The reaction mixture is stirred at 130° C. overnight. The mixture is cooled to rt, diluted with H2O; and extracted with EtOAc (3×20 ml). The organic layers are dried (Na2SO4), filtered and purified by HPLC to give title compound (32 mg, 0.087 mmol, 8%). 1H-NMR (CDCl3), δ 0.93 (t, J=7.2 Hz, 6H), 1.91 (m, 4H), 2.15 (s, 3H), 2.58 (s, 3H), 3.36 (m, 1H), 6.91 (s, 1H), 7.08 (d, J=5.3 Hz, 1H), 7.55 (d, J=5.5 Hz, 1H) ppm. ES-MS (m/z): calcd for C19H20F3N3S (M+H)+: 367.44; found: 368.1.

Workup

  1. temperatureTo a dry 10 ml round bottom flask with reflux condenser
  2. customThe mixture is degassed with bubbling N2 for 15 min
  3. temperatureThe mixture is cooled to rt
  4. extractionand extracted with EtOAc (3×20 ml)
  5. dry with materialThe organic layers are dried (Na2SO4)
  6. filtrationfiltered
  7. custompurified by HPLC

Sources & evidence

ORD record
ord-3a3da283af4146518aa1767b10301067
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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