Acetyl chloride → N-[4-(2-Amino-2-methyl-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-4-chloro-benzamide

4-Chlorobenzoyl chloride (280-, 0.22 mmol) was added to a solution of 3-(2-methyl-2H-pyrazol-3-yl)-4-(2-methyl-2-nitropropoxy)aniline (58 mg, 0.20 mmol) and N,N-diisopropylethylamine 0.22 mmol) in dichloromethane (0.5 mL) and the mixture was stirred at room temperature. After 1 h, the mixture was diluted with dichloromethane, washed with 0.5M citric acid and saturated sodium bicarbonate, dried with sodium sulfate, filtered, and evaporated to dryness. The residue was dissolved in methanol (0.5 mL) and acetyl chloride (71 μl, 1.0 mmol) was added slowly while stirring. Zinc dust (65 mg, 1.0 mmol) was added in small portions, and the mixture was stirred at 55° C. After 2 h, the mixture was allowed to cool to room temperature, and diluted with methanol. The white precipitate was removed by filtration and washed with methanol. The combined washings were evaporated to dryness. The residue was suspended in 1M HCl, the solution was cooled on an ice bath, and made alkaline with ammonium hydroxide. The solution was extracted with ethyl acetate, and the extract was washed with brine, dried with sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by RP-HPLC. The trifluoroacetate salt was dissolved in a mixture of ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with brine, dried with sodium sulfate, and evaporated to dryness to afford the free base. The free base was dissolved in mixture of methanol and acetyl chloride (350-, 0.5 mmol) and the solution was evaporated to dryness to give the title compound as a hydrochloride salt (44 mg, 45%). LCMS m/z (%)=401.3 (M+H 37Cl 13.1%), 399.2 (M+H 35Cl 31.8%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.19 (s, 6H), 3.70 (s, 3H), 3.92 (s, 2H), 6.37 (d, J=1.77 Hz, 1H), 7.25 (d, J=9.09 Hz, 1H), 7.50 (d, J=1.77 Hz, 1H), 7.59-7.65 (m, 2H), 7.73 (d, J=2.53 Hz, 1H), 7.87 (dd, J=8.97, 2.65 Hz, 1H), 7.95-8.01 (m, 2H), 8.03 (s, 3H), 10.39 (s, 1H).

1. washwashed with 0.5M citric acid and saturated sodium bicarbonate
2. dry with materialdried with sodium sulfate
3. filtrationfiltered
4. customevaporated to dryness
5. dissolutionThe residue was dissolved in methanol (0.5 mL)
6. stirringwhile stirring
7. stirringthe mixture was stirred at 55° C
8. waitAfter 2 h
9. temperatureto cool to room temperature
10. customThe white precipitate was removed by filtration
11. washwashed with methanol
12. customThe combined washings were evaporated to dryness
13. temperaturethe solution was cooled on an ice bath
14. extractionThe solution was extracted with ethyl acetate
15. washthe extract was washed with brine
16. dry with materialdried with sodium sulfate
17. filtrationfiltered
18. customevaporated to dryness
19. customThe crude product was purified by RP-HPLC
20. dissolutionThe trifluoroacetate salt was dissolved in a mixture of ethyl acetate and saturated sodium bicarbonate
21. washThe organic layer was washed with brine
22. dry with materialdried with sodium sulfate
23. customevaporated to dryness
24. customto afford the free base
25. customthe solution was evaporated to dryness

ORD record

ord-a475023dc9b642e4affa788ffa5adc40

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328107B2