Cesium carbonate → 8-(1-Ethyl-propyl)-3-(5-fluoro-3-methyl-benzo[b]thiophen-2-yl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine

HRID 226044Notes

Reaction equation

HRID 226044 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:25][C:24]2[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:23]=2[C:22]=1[CH3:31].C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CN1C(=O)CCC1.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]>[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13]([C:21]3[S:25][C:24]4[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:23]=4[C:22]=3[CH3:31])=[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 667212022-Bromo-5-fluoro-3-methylbenzo[b]thiopheneHCID 688409078-(1-Ethyl-propyl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine

Product 1

HCID 577526508-(1-Ethyl-propyl)-3-(5-fluoro-3-methyl-benzo[b]thiophen-2-yl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazineYield 10%

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 (150 mg, 0.690 mmol), 2-bromo-5-fluoro-3-methyl-benzo[b]thiophene (186.1 mg, 0.759 mmol), and Cs2CO3 (472 mg, 1.45 mmol) in NMP (1.1 ml). The mixture is degassed with bubbling N2 for 15 min. Then add Pd2(dba)3 (32 mg, 0.0345 mmol) and PPh3 (36.2 mg, 0.138 mmol). Heat the reaction mixture at 130° C. and stir overnight. Dilute with H2O; extract with EtOAc (3×20 ml); dried (Na2SO4), filter and purify by HPLC to give title compound (29.5 mg, 0.068 mmol, 10%). 1H NMR (CDCl3): 0.931 (t, J=7.6 Hz, 6H), 1.912 (m, 4H), 2.286 (s, 3H), 2.552 (s, 3H), 3.386 (m, 1H), 6.877 (s, 1H), 7.224 (td, J=2.4, 9.0 Hz, 1H), 7.50 (dd, J=2.9, 9.8 Hz, 1H), 7.842 (dd, J=4.9, 9.0 Hz, 1H) ppm. ES-MS (m/z): calcd for C22H21F4N3S (M+H)+: 435.39. found: 436.2.

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. extractionextract with EtOAc (3×20 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfilter
  6. custompurify by HPLC

Sources & evidence

ORD record
ord-417002ea858b4115a604cba58048daec
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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