Dimethylformamide → N-(6-(6-chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

HRID 1162445Notes

Reaction equation

HRID 1162445 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].CN(C=O)C.Cl[C:49]1[CH:50]=[CH:51][C:52]2[N:53]([CH:55]=[C:56]([NH:58][C:59](=[O:61])[CH3:60])[N:57]=2)[N:54]=1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([C:49]2[CH:50]=[CH:51][C:52]3[N:53]([CH:55]=[C:56]([NH:58][C:59](=[O:61])[CH3:60])[N:57]=3)[N:54]=2)=[CH:3][C:4]=1[NH:9][S:10]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)(=[O:12])=[O:11]

Participants

9

Reactant 6

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 53363354N-(5-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamideHCID 59519510N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide

Product 1

HCID 44124863N-(6-(6-chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 25-mL, round-bottomed flask was added N-(5-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide (0.15 g, 0.41 mmol), bis(pinacolato)diboron (0.16 g, 0.62 mmol), potassium acetate (0.16 g, 1.6 mmol) and 1,4-dioxane (4.0 mL). The mixture was carefully evacuated and backfilled with N2. To the solution was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (0.030 g, 0.041 mmol). The mixture was carefully evacuated and backfilled with N2 again then stirred at 90° C. for 6 h. The reaction mixture was cooled to rt and treated with DMF (4.0 mL, 52 mmol), N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide (0.055 g, 0.26 mmol) and 2.0 M aq. sodium carbonate (0.78 mL, 1.6 mmol). The mixture was carefully evacuated and backfilled with N2. To the solution was added trans-dichlorobis(triphenylphosphine)palladium(II) (0.018 g, 0.026 mmol) and then the solution was carefully evacuated and backfilled with N2 again. The mixture was stirred at 90° C. for 16 hours then poured into aq. NaCl (100 mL) and extracted with 25% iPrOH/CHCl3 (3×75 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to remove the DMF. The solution was then taken up in MeOH/CH2Cl2 and concentrated onto silica. Purification by silica gel chromatography (0.5 to 5.0% MeOH (2 M in NH3)/CH2Cl2) afforded the title compound as a yellow solid. MS (ESI pos. ion) m/z: 461 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.96 (s, 1H), 10.57 (s, 1H), 8.92 (d, J=2.2 Hz, 1H), 8.31-8.36 (m, 2H), 8.13 (d, J=9.4 Hz, 1H), 7.80-7.88 (m, 3H), 7.39-7.48 (m, 2H), 2.13 (s, 3H).

Workup

  1. customThe mixture was carefully evacuated
  2. customThe mixture was carefully evacuated
  3. temperatureThe reaction mixture was cooled to rt
  4. customThe mixture was carefully evacuated
  5. customthe solution was carefully evacuated
  6. stirringThe mixture was stirred at 90° C. for 16 hours
  7. additionthen poured into aq. NaCl (100 mL)
  8. extractionextracted with 25% iPrOH/CHCl3 (3×75 mL)
  9. dry with materialThe combined extracts were dried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customto remove the DMF
  12. concentrationconcentrated onto silica
  13. customPurification by silica gel chromatography (0.5 to 5.0% MeOH (2 M in NH3)/CH2Cl2)

Sources & evidence

ORD record
ord-a2cf58bf683441439bf2390a7ed0ab20
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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