Sodium Carbonate → 4-(6-(2-(2,5-Difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile

HRID 1890690Notes

Reaction equation

HRID 1890690 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[C:7]([C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][C:10]=1[F:18])#[N:8].Br[C:20]1[N:24]2[N:25]=[C:26]([N:29]3[CH2:33][CH2:32][CH2:31][CH:30]3[C:34]3[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=3[F:41])[CH:27]=[CH:28][C:23]2=[N:22][CH:21]=1>O1CCOCC1.O>[F:41][C:35]1[CH:36]=[CH:37][C:38]([F:40])=[CH:39][C:34]=1[CH:30]1[CH2:31][CH2:32][CH2:33][N:29]1[C:26]1[CH:27]=[CH:28][C:23]2[N:24]([C:20]([C:12]3[CH:13]=[CH:14][C:9]([C:7]#[N:8])=[C:10]([F:18])[CH:11]=3)=[CH:21][N:22]=2)[N:25]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 583354643-Bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine

Product 1

HCID 445207774-(6-(2-(2,5-Difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

In step 12-1, [Pd(Dppf)2]Cl2 (90 mg, 0.11 mmol), sodium carbonate (0.41 g, 3.9 mmol), and 4-cyano-3-fluorophenylboronic acid (0.36 g, 2.2 mmol) were added to a solution of 3-bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (6-6) (0.42 g, 1.1 mmol) in 3 mL of dioxane and 1 mL of DI water. The reaction mixture was heated in a microwave for twenty minutes at 150° C., and the slurry was then cooled to room temperature and filtered through a 0.2 μM nylon fit. The solvent was removed from the mother liquor and the remaining residue was reconstituted in dichloromethane (DCM). This solution was loaded onto a 12 g silica gel column and eluted using a 0-10% methanol in DCM gradient over 30 minutes. The solvent was removed from the desired fractions to yield 4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile. m/z=420.2 [M+1].

Workup

  1. temperaturethe slurry was then cooled to room temperature
  2. filtrationfiltered through a 0.2 μM nylon fit
  3. customThe solvent was removed from the mother liquor
  4. washeluted
  5. customover 30 minutes
  6. customThe solvent was removed from the desired fractions

Sources & evidence

ORD record
ord-2bbd0266b16245caadff03b3e497a402
Source dataset
uspto-grants-2013_08
Patent number
US08507488B2

Reaction notes

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