Sodium Carbonate → n-(5-(2-Aminoimidazo[1,2-a]pyridin-6-yl)-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide

HRID 1162464Notes

Reaction equation

HRID 1162464 reaction equation
[Cl:1][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](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.[CH:28]1[C:36](Br)=[CH:35][N:34]2[C:30](=[N:31][CH:32]=[CH:33]2)[CH:29]=1.COC1C2C=CNC=2N=C(N)[N:41]=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.CS(C)=O>[NH2:41][C:32]1[N:31]=[C:30]2[CH:29]=[CH:28][C:36]([C:5]3[CH:6]=[C:7]([NH:8][S:9]([C:12]4[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=4)(=[O:10])=[O:11])[C:2]([Cl:1])=[N:3][CH:4]=3)=[CH:35][N:34]2[CH:33]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 53363355n-[2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-4-fluorobenzene-1-sulfonamideHCID 1317283986-bromoH-imidazo[1,2-a]pyridin 2-amine

Product 1

HCID 44125376n-(5-(2-Aminoimidazo[1,2-a]pyridin-6-yl)-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamideYield 22.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

To a 10 mL round-bottomed flask was added N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide (0.150 g, 0.363 mmol) (Step 2, Example 48), 6-bromoH-imidazo[1,2-a]pyridin-2-amine (0.0700 g, 0.330 mmol) (Step 4, Example 28), DMSO (3.00 mL), and sodium carbonate (0.990 mL, 1.98 mmol, 2 M). The mixture was carefully evacuated and backfilled with N2. To the mixture was added trans-dichlorobis(triphenylphosphine)palladium(II) (0.0232 g, 0.0330 mmol, Strem Chemical, Inc., Newburyport, Mass.). Again, the mixture was carefully evacuated and backfilled with N2. The mixture was stirred at 95° C. for 3 h. After cooling to rt, the mixture was poured into pH 4.8 buffer (3 M sodium acetate solution pH adjusted to 4.8, Teknova, Hollister, Mass.) diluted with water. The solution was filtered and the filtercake was washed with water and then 50% CH2Cl2/hexane. The aqueous washings were extracted with 25% iPrOH/CHCl3 and the extracts were combined with the filtercake. The combined material was concentrated to remove all of the solvents and the residue was taken up in MeOH/CH2Cl2 and concentrated onto silica. Purification by silica gel chromatography (2.0 to 9.0% MeOH/CH2Cl2) afforded the title compound as a yellow solid (0.0307 g, 22%). MS (ESI, positive ion) m/z: 418 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.08 (s, 1H), 7.34 (br s, 3H), 7.38-7.44 (m, 3H), 7.60 (br s, 2H), 7.78-7.84 (m, 3H), 7.97 (d, J=2.2 Hz, 1H), 8.49 (d, J=2.0 Hz, 1H), 8.77 (s, 1H).

Workup

  1. customThe mixture was carefully evacuated
  2. customAgain, the mixture was carefully evacuated
  3. temperatureAfter cooling to rt
  4. additionthe mixture was poured into pH 4.8 buffer (3 M sodium acetate solution
  5. addition) diluted with water
  6. filtrationThe solution was filtered
  7. washthe filtercake was washed with water
  8. extractionThe aqueous washings were extracted with 25% iPrOH/CHCl3
  9. concentrationThe combined material was concentrated
  10. customto remove all of the solvents
  11. concentrationconcentrated onto silica
  12. customPurification by silica gel chromatography (2.0 to 9.0% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-8d8ddff85aeb4e3a804eed36602b14b3
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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