Sodium Carbonate → HCID 178474394, compound

HRID 1162466Notes

Reaction equation

HRID 1162466 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+].Br[C:44]1[CH:56]=[CH:55][C:47]2[NH:48][C:49]([NH:51][C:52](=[O:54])[CH3:53])=[N:50][C:46]=2[CH:45]=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>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([C:56]2[CH:44]=[CH:45][C:46]3[NH:50][C:49]([NH:51][C:52](=[O:54])[CH3:53])=[N:48][C:47]=3[CH:55]=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 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 53363354N-(5-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamideHCID 178474391HCID 178474391, compound

Product 1

HCID 178474394HCID 178474394, compoundYield 15.2%

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-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide (0.150 g, 0.410 mmol) (Step 1, Example 48), bis(pinacolato)diboron (0.156 g, 0.615 mmol, Aldrich, St, Louis, Mo.), potassium acetate (0.161 g, 1.64 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, Strem Chemical, Inc., Newburyport, Mass.). The mixture was carefully evacuated and backfilled with N2 again. The mixture was stirred at 90° C. for 6 h. The reaction mixture was cooled to rt and to it was added DMF (4.0 mL), N-(5-bromo-1H-benzo[d]imidazol-2-yl)acetamide (0.080 g, 0.31 mmol) and aq sodium carbonate (0.79 mL, 1.6 mmol, 2 M). The mixture was carefully evacuated and backfilled with N2. To the mixture was added trans-dichlorobis(triphenylphosphine)palladium(II) (0.022 g, 0.031 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 16 h and then, after cooling to rt, was poured into aq. NaCl (100 mL) and extracted with 25% iPrOH/CHCl3 (3×75 mL). The combined extracts were dried (Na2SO4) and concentrated. The material 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 white solid (0.0217 g, 15%). MS (ESI, positive ion) m/z: 460 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.18 (s, 3H), 7.37 (br s, 1H), 7.44 (t, J=8.8 Hz, 2H), 7.56 (br s, 1H), 7.70 (br s, 1H), 7.83 (dd, J=8.8, 5.3 Hz, 2H), 7.91 (s, 1H), 8.56 (br s, 1H), 10.44 (br s, 1H), 11.62 (br s, 1H), 12.16 (br s, 1H).

Workup

  1. customThe mixture was carefully evacuated
  2. customThe mixture was carefully evacuated
  3. temperatureThe reaction mixture was cooled to rt and to it
  4. customThe mixture was carefully evacuated
  5. customOnce again the mixture was carefully evacuated
  6. stirringThe mixture was stirred at 90° C. for 16 h
  7. temperatureafter cooling to rt
  8. additionwas poured into aq. NaCl (100 mL)
  9. extractionextracted with 25% iPrOH/CHCl3 (3×75 mL)
  10. dry with materialThe combined extracts were dried (Na2SO4)
  11. concentrationconcentrated
  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-ff1136683c90473796faccef2a65389e
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

Loading…