Ammonium Chloride → Irsenontrine

Temperature

100 °C

Ethyl 5-[4-(2-methoxy-3,5-dimethylpyridin-4-yl)-2-nitrophenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate (1.1 g) was suspended in ethanol (13 mL) Iron powder (280 mg) and a saturated aqueous ammonium chloride solution (3 mL) were added to the solution, and the mixture was stirred at 100° C. for 3.5 hours. The reaction mixture was cooled to room temperature and then filtered through Celite™. The filtrate was partitioned by adding ethyl acetate (100 mL) and water (50 mL). The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetic acid (2 mL), followed by stirring at 50° C. After four hours, the reaction mixture was cooled to mom temperature, and water (20 mL) was added. The precipitated solid was collected by filtration. 1-propanol (10 ml) and water (1.5 mL) were added to the resulting solid which was dissolved with heating under reflux. The solution was cooled with ice water. After one hour, the precipitated solid was collected by filtration and washed with MTBE (5 mL) to give the title compound (780 mg).

1. temperatureThe reaction mixture was cooled to room temperature
2. filtrationfiltered through Celite™
3. customThe filtrate was partitioned
4. additionby adding ethyl acetate (100 mL) and water (50 mL)
5. washThe organic layer was washed with brine
6. dry with materialdried over anhydrous magnesium sulfate
7. customThe desiccant was removed by filtration
8. concentrationthe filtrate was concentrated under reduced pressure
9. dissolutionThe resulting residue was dissolved in acetic acid (2 mL)
10. stirringby stirring at 50° C
11. waitAfter four hours
12. temperaturethe reaction mixture was cooled to mom temperature, and water (20 mL)
13. additionwas added
14. filtrationThe precipitated solid was collected by filtration
15. addition1-propanol (10 ml) and water (1.5 mL) were added to the resulting solid which
16. dissolutionwas dissolved
17. temperaturewith heating
18. temperatureunder reflux
19. temperatureThe solution was cooled with ice water
20. waitAfter one hour
21. filtrationthe precipitated solid was collected by filtration
22. washwashed with MTBE (5 mL)

ORD record

ord-6b25ff0940cf4e3aa1be70a3107952bf

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08563565B2