Dimethyl Sulfoxide → HCID 58072465, compound

Temperature

-78 °C

To a solution of oxalyl chloride (0.175 mL, 2.07 mmol) in THF (7.5 mL) was added DMSO (0.294 mL, 4.14 mmol) at −78° C. To the suspension was added a solution of 3-(hydroxymethyl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (509 mg, 1.88 mmol) in THF (7.5 mL) at −78° C. The suspension was stirred at −78° C. for 1 h. To the mixture was added Et3N (1.05 mL, 7.52 mmol) at −78° C. The mixture was gradually warmed to room temperature, stirred at room temperature for 18 h, diluted with 1 M HCl aqueous solution, extracted with EtOAc, washed with saturated NaHCO3 aqueous solution and brine, dried over Na2SO4, filtered, concentrated in vacuo and purified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100 and EtOAc/MeOH=100/0 to 70/30). To a solution of oxalyl chloride (0.477 mL, 5.64 mmol) in THF (19 mL) was added DMSO (0.801 mL, 11.3 mmol) at −78° C. To the suspension was added a mixture of the above residue in THF (9.5 mL) at −78° C. The suspension was stirred at −78° C. for 2 h. To the mixture was added Et3N (3.14 mL, 22.6 mmol) at −78° C. The mixture was gradually warmed to room temperature, stirred at room temperature for 17 h, diluted with 1 M HCl aqueous solution, extracted with EtOAc, washed with saturated NaHCO3 aqueous solution and brine, dried over Na2SO4, filtered, concentrated in vacuo and purified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100) to yield the title compound (257 mg, 51% yield) as a yellow solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 6.87 (1H, d, J=8.2 Hz), 7.81-7.91 (2H, m), 8.08-8.15 (1H, m), 8.16 (1H, s), 8.98 (1H, d, J=8.0 Hz), 10.07 (1H, s).

1. temperatureThe mixture was gradually warmed to room temperature
2. stirringstirred at room temperature for 18 h
3. extractionextracted with EtOAc
4. washwashed with saturated NaHCO3 aqueous solution and brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. custompurified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100 and EtOAc/MeOH=100/0 to 70/30)
9. additionTo the suspension was added
10. stirringThe suspension was stirred at −78° C. for 2 h
11. temperatureThe mixture was gradually warmed to room temperature
12. stirringstirred at room temperature for 17 h
13. extractionextracted with EtOAc
14. washwashed with saturated NaHCO3 aqueous solution and brine
15. dry with materialdried over Na2SO4
16. filtrationfiltered
17. concentrationconcentrated in vacuo
18. custompurified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100)

ORD record

ord-a1c215be4df94408ac024cdf79cd3497

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08435995B2