Sodium Carbonate → 4-Fluoro-N-(5-imidazo[1,2-a]pyridin-3-yl-3-pyridinyl)benzenesulfonamide

HRID 1025386Notes

Reaction equation

HRID 1025386 reaction equation
Cl[C:2]1[C:7]([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:6][C:5]([C:19]2[N:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]3=[N:21][C:20]=2C)=[CH:4][N:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].C1C=CN2C(=NC=C2Br)C=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O>[F:18][C:15]1[CH:14]=[CH:13][C:12]([S:9]([NH:8][C:7]2[CH:2]=[N:3][CH:4]=[C:5]([C:19]3[N:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]4=[N:21][CH:20]=3)[CH:6]=2)(=[O:11])=[O:10])=[CH:17][CH:16]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 3279513-Bromoimidazo[1,2-a]pyridineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 46913214N-(2-Chloro-5-(2-methylimidazo[1,2-a]pyridin-3-yl)-3-pyridinyl)-4-fluorobenzenesulfonamide

Product 1

HCID 469133104-Fluoro-N-(5-imidazo[1,2-a]pyridin-3-yl-3-pyridinyl)benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

N-(5-(H-imidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide. A suspension of N-(5-bromopyridin-3-yl)-4-fluorobenzenesulfonamide (from Example 1) (200 mg, 604 μmol), bis(pinacolato)diboron (169 mg, 664 μmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(ii)dichloride dichloromethane complex (44.2 mg, 60.4 μmol), potassium acetate (119 mg, 1208 μmol) in 1,4-dioxane (2.5 mL) was sparged with argon for 5 min, appropriately sealed, then heated to 120° C. for 1 h. The reaction vessel was then charged with 3-bromoH-imidazo[1,2-a]pyridine (Alfa Aesar (USA), 149 mg, 755 μmol), sodium carbonate (192 mg; 1.82 mmol) and water (0.5 mL)-sparged with argon-then heated to 100° C. for 3 h. The reaction was then partitioned between 9:1 CHCl3/i-Pr (25 mL) and 5% NaHCO3 (10 mL). The remaining residue in the reaction vessel was dissolved in DMF (3 mL) and added to the separatory funnel. The aqueous layer was then adjusted to a pH of about 8 with 5M HCl, and aqueous further extracted with 9:1 CHCl3/i-Pr (10 mL). The combined organics were dried over MgSO4 then concentrated under reduced pressure. The product was purified on silica (24 g) eluting with 3 to 8% of 2M NH3 in MeOH/CH2Cl2. Product then further purified on reverse phase HPLC eluting with water/acetonitrile (0.1% TFA). The desired fractions were then concentrated under reduced pressure, dissolved in CH3OH/CH2Cl2 (1:1; 5 mL), and stirred with Si-Carbonate (250 mg; 0.2 mmol) for 15 min. The filtrate was isolated by filtration then concentrated to a white solid. MS (ESI positive) m/z: calcd exact mass for C18H13FN4O2S: 368.1; found 369.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.97-7.04 (m, 1H) 7.33-7.39 (m, 1H) 7.41-7.49 (m, 2H) 7.70 (d, J=9.00 Hz, 1H) 7.73 (t, J=2.15 Hz, 1H) 7.84 (s, 1H) 7.87-7.93 (m, 2H) 8.31 (d, J=2.35 Hz, 1H) 8.36 (d, J=6.85 Hz, 1H) 8.59 (d, J=1.76 Hz, 1H) 10.79 (br. s., 1H).

Workup

  1. customwas sparged with argon for 5 min
  2. customappropriately sealed
  3. temperaturewith argon-then heated to 100° C. for 3 h
  4. customThe reaction was then partitioned between 9:1 CHCl3/i-Pr (25 mL) and 5% NaHCO3 (10 mL)
  5. dissolutionThe remaining residue in the reaction vessel was dissolved in DMF (3 mL)
  6. additionadded to the separatory funnel
  7. extractionaqueous further extracted with 9:1 CHCl3/i-Pr (10 mL)
  8. dry with materialThe combined organics were dried over MgSO4
  9. concentrationthen concentrated under reduced pressure
  10. customThe product was purified on silica (24 g)
  11. washeluting with 3 to 8% of 2M NH3 in MeOH/CH2Cl2
  12. customProduct then further purified on reverse phase HPLC
  13. washeluting with water/acetonitrile (0.1% TFA)
  14. concentrationThe desired fractions were then concentrated under reduced pressure
  15. dissolutiondissolved in CH3OH/CH2Cl2 (1:1; 5 mL)
  16. customThe filtrate was isolated by filtration
  17. concentrationthen concentrated to a white solid

Sources & evidence

ORD record
ord-7d23bbf6b97c48df9092806627cbbdc7
Source dataset
uspto-grants-2014_05
Patent number
US08729074B2

Reaction notes

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