Triethylamine → HCID 24985807, compound

To a solution of (1Z)-2-[4-chloro-5-cyano-2-(difluoromethyl)-1H-indol-1-yl]-N-hydroxyethanimidamide (0.011 g, 0.035 mmol) in anhydrous THF (1.5 mL), under N2, was added picolinoyl chloride hydrochloride (0.0066 g, 0.037 mmol) and Et3N (0.0078 g, 0.077 mmol). The mixture was stirred at rt for 30 min. The reaction was monitored by TLC and additional acid chloride (0.003 g, 0.018 mmol) and Et3N (0.0035 g, 0.035 mmol) were added and stirring continued at rt for 1 h. The mixture was then heated in a microwave at 120° C. for 20 min, and subsequently at 150° C. for 2 h. Upon cooling, the mixture was partitioned between EtOAc and 0.1N HCl. The organic phase was washed with 0.1N HCl, sat'd NaHCO3 solution and sat'd brine, dried (Na2SO4), and concentrated in vacuo. The residue was purified by flash chromatography (5-50% EtOAc-hexanes gradient), followed by a second purification by radial chromatography (5-70% EtOAc-hexanes gradient). The product was crystallized from CH2Cl2-hexanes to afford the title compound as a white solid (0.005 g, 38% yield): MS (ES) m/z 386 (M+1).

1. additionwere added
2. stirringstirring
3. waitcontinued at rt for 1 h
4. temperatureThe mixture was then heated in a microwave at 120° C. for 20 min
5. waitsubsequently at 150° C. for 2 h
6. temperatureUpon cooling
7. customthe mixture was partitioned between EtOAc and 0.1N HCl
8. washThe organic phase was washed with 0.1N HCl
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated in vacuo
11. customThe residue was purified by flash chromatography (5-50% EtOAc-hexanes gradient)
12. customfollowed by a second purification by radial chromatography (5-70% EtOAc-hexanes gradient)
13. customThe product was crystallized from CH2Cl2-hexanes

ORD record

ord-26a7289488104f3d92cdd8852a9d9381

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07572820B2