Sodium Carbonate → HCID 44124753, compound

HRID 1162443Notes

Reaction equation

HRID 1162443 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:5]=[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+].Cl[C:43]1[CH:44]=[CH:45][C:46]2[N:47]([CH:49]=[C:50]([NH:52][C:53](=[O:55])[CH3:54])[N:51]=2)[N:48]=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.CN(C=O)C.O1CCOCC1>[F:18][C:15]1[CH:16]=[CH:17][C:12]([S:9]([NH:8][C:4]2[CH:3]=[C:2]([C:43]3[CH:44]=[CH:45][C:46]4[N:47]([CH:49]=[C:50]([NH:52][C:53](=[O:55])[CH3:54])[N:51]=4)[N:48]=3)[CH:7]=[N:6][CH:5]=2)(=[O:11])=[O:10])=[CH:13][CH:14]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 59519510N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamideHCID 66671708HCID 66671708, compound

Product 1

HCID 44124753HCID 44124753, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 25-mL, round-bottomed flask was added N-(5-bromopyridin-3-yl)-4-fluorobenzenesulfonamide (0.15 g, 0.45 mmol), bis(pinacolato)diboron (0.17 g, 0.68 mmol), potassium acetate (0.18 g, 1.8 mmol) and 1,4-dioxane (4.0 mL). The mixture was carefully evacuated and backfilled with N2. To this mixture was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (0.033 g, 0.045 mmol, Strem Chemicals, Inc., Newburyport, Mass.). The mixture was carefully evacuated and backfilled with N2. The mixture was stirred at 90° C. for 19 h then allowed to cool to room temperature. To the solution was added DMF (4.0 mL), N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide (Example 1, Step 4) (0.075 g, 0.36 mmol) and aq. Na2CO3 (0.89 mL, 1.8 mmol, 2 M). The mixture was carefully evacuated and backfilled with N2. To the mixture was added trans-dichlorobis(triphenylphosphine)palladium (II) (0.025 g, 0.036 mmol, Strem Chemical, Inc., Newburyport, Mass.). Once again the mixture was carefully evacuated and backfilled with N2. The mixture was stirred at 90° C. for 2 h and then was allowed to cool to room temperature. The solution was poured into water (100 mL), extracted with 25% iPrOH/CHCl3 (3×75 mL) and the combined extracts were washed with brine, dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (2 to 8% MeOH (2 M in NH3)/CH2Cl2) afforded the title compound as a tan solid. MS (ESI pos. ion) m/z: 427 (M+1). 1H NMR (400 MHz, DMSO-d6): δ 10.95 (s, 1H), 10.84 (s, 1H), 8.92 (d, J=1.8 Hz, 1H), 8.41 (d, J=2.5 Hz, 1H), 8.31 (s, 1H), 8.09-8.13 (m, 2H), 7.88-7.91 (m, 2H), 7.76 (d, J=9.4 Hz, 1H), 7.42 (d, J=8.8 Hz, 2H), 2.12 (s, 3H).

Workup

  1. customThe mixture was carefully evacuated
  2. customThe mixture was carefully evacuated
  3. temperatureto cool to room temperature
  4. customThe mixture was carefully evacuated
  5. customOnce again the mixture was carefully evacuated
  6. stirringThe mixture was stirred at 90° C. for 2 h
  7. temperatureto cool to room temperature
  8. additionThe solution was poured into water (100 mL)
  9. extractionextracted with 25% iPrOH/CHCl3 (3×75 mL)
  10. washthe combined extracts were washed with brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated onto silica
  13. customPurification by silica gel chromatography (2 to 8% MeOH (2 M in NH3)/CH2Cl2)

Sources & evidence

ORD record
ord-4d936789730f4a9fbf3b056f2c33f897
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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