Sodium Carbonate → HCID 57584976, compound

Temperature

90 °C

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, Aldrich, St. Louis. MO), potassium acetate (0.18 g, 1.8 mmol) and 1,4-dioxane (4.0 ml). The mixture was carefully evacuated and backfilled with N2 and then dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.033 g, 0.045 mmol, Strem, Newburyport, Mass.) was added. The mixture was carefully evacuated and backfilled with N2 again. The mixture was stirred at 90° C. for 19 hours and then allowed to cool to rt. To the mixture was added DMF (4.0 ml), N-(5-chlorothiazolo[5,4-b]pyridin-2-yl)acetamide (0.075 g, 0.33 mmol) and 2 M sodium carbonate (0.82 ml, 1.7 mmol). The mixture was carefully evacuated and backfilled with N2 and then trans-dichlorobis(triphenylphosphine)palladium (II) (0.023 g, 0.033 mmol, Strem) was added. The mixture was carefully evacuated and backfilled with N2 and then stirred at 90° C. for 18 h. The mixture was allowed to cool to room temperature and then poured into water (100 mL) and extracted with 25% iPrOH/CHCl3 (4×50 mL). The combined extracts were dried (Na2SO4) and concentrated. The residue was taken up in CH2Cl2/MeOH and concentrated onto silica. Purification by silica gel chromatography (3.0 to 10% MeOH (2 M in NH3)/CH2Cl2) afforded a brown solid. This was further purified by Prep-HPLC (Phenomenex Synergi 4u MAX-RP 80A 150×21.20 nm n, 00F-4337-P0, 2 to 100% CH3CN (0.1% TFA)/H2O (0.1% TFA) over 15 min then 100% CH3CN for 5 minutes at 20 ml/min) with the fractions containing suspected product concentrated to afford the title compound as a tan solid (0.012 g, 6.3% yield). MS (ESI pos. ion) m/z: 444 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.55 (s, 1H), 10.71 (s, 1H), 9.00 (d, J=1.8 Hz, 1H), 8.36 (d, J=2.5 Hz, 1H), 8.17-8.22 (m, 2H), 8.07 (d, J=8.6 Hz, 1H), 7.85-7.90 (m, 2H), 7.39-7.45 (m, 2H), 2.24 (s, 3H).

1. customThe mixture was carefully evacuated
2. customThe mixture was carefully evacuated
3. temperatureto cool to rt
4. customThe mixture was carefully evacuated
5. customThe mixture was carefully evacuated
6. stirringstirred at 90° C. for 18 h
7. temperatureto cool to room temperature
8. additionpoured into water (100 mL)
9. extractionextracted with 25% iPrOH/CHCl3 (4×50 mL)
10. dry with materialThe combined extracts were dried (Na2SO4)
11. concentrationconcentrated
12. concentrationconcentrated onto silica
13. customPurification by silica gel chromatography (3.0 to 10% MeOH (2 M in NH3)/CH2Cl2)
14. customafforded a brown solid
15. customThis was further purified by Prep-HPLC (Phenomenex Synergi 4u MAX-RP 80A 150×21.20 nm n, 00F-4337-P0, 2 to 100% CH3CN (0.1% TFA)/H2O (0.1% TFA) over 15 min
16. addition100% CH3CN for 5 minutes at 20 ml/min) with the fractions containing suspected product
17. concentrationconcentrated

ORD record

ord-3a646b40a1c547c78c9582418dbe3991

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07928140B2