Hydrochloric Acid → HCID 71263611, compound

Temperature

80 °C

To a solution of 6-(N-(4-bromo-3-(methylsulfonyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (200 mg, 0.315 mmol) in 1,4-Dioxane (2 mL) wad added 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (400 mg, 1.574 mmol), potassium acetate (154 mg, 1.574 mmol) and Pd(II)(dppf)Cl2 DCM complex (12.85 mg, 0.016 mmol). The mixture was stirred under nitrogen at 80° C. After 4 hours the mixture was cooled to RT and diluted with EtOAc (10 mL). The resulting solution was washed with water, saturated brine, and dried over sodium sulfate. After evaporation of the solvent, the crude residue was dissolved in 10 mL of THF and the resulting solution cooled in an ice water bath. The solution was treated with 1N aqueous HCl (1.574 mL, 1.574 mmol) followed by sodium periodate (135 mg, 0.629 mmol). The mixture was stirred at 0° C. for 20 minutes and then allowed to warm to RT. After 18 hours, the mixture was partitioned between water and EtOAc and the phases separated. The aqueous solution was extracted with EtOAc. The combined EtOAc solutions were washed with 5% aqueous sodium bisulfite, saturated brine, dried over sodium sulfate and concentrated to dryness at reduced pressure. The residue was subjected to HPLC purification (ACN: Water—0.1% Formic acid) to provide the pure product (12 mg, 6.4%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.97 (br. s., 2H), 7.87 (d, J=5.37 Hz, 2H), 7.56-7.64 (m, 2H), 7.49 (s, 1H), 7.15-7.24 (m, 2H), 6.15-6.37 (m, 1H), 5.77-5.92 (m, 1H), 3.30 (s, 3H), 3.13 (br. s., 3H), 3.00 (d, J=2.34 Hz, 3H), 1.91-2.10 (m, 1H), 1.18-1.34 (m, 1H), 0.95-1.10 (m, 1H), 0.83-0.93 (m, 1H), 0.69-0.83 (m, 1H), 0.44-0.61 (m, 1H). LCMS (m/z, ES+)=601 (M+H+).

1. temperatureAfter 4 hours the mixture was cooled to RT
2. washThe resulting solution was washed with water, saturated brine
3. dry with materialdried over sodium sulfate
4. customAfter evaporation of the solvent
5. dissolutionthe crude residue was dissolved in 10 mL of THF
6. temperaturethe resulting solution cooled in an ice water bath
7. stirringThe mixture was stirred at 0° C. for 20 minutes
8. temperatureto warm to RT
9. customthe mixture was partitioned between water and EtOAc
10. customthe phases separated
11. extractionThe aqueous solution was extracted with EtOAc
12. washThe combined EtOAc solutions were washed with 5% aqueous sodium bisulfite, saturated brine
13. dry with materialdried over sodium sulfate
14. concentrationconcentrated to dryness at reduced pressure
15. customThe residue was subjected to HPLC purification (ACN: Water—0.1% Formic acid)

ORD record

ord-74deb2eea95b419483fec5dd64c61284

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09119868B2