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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence