Dimethylformamide → 1-(4-chlorophenyl)-5-(propan-2-yl)-1H-pyrazol-4-amine

To a solution of 1-(4-chlorophenyl)-5-isopropylpyrazole-4-carboxylic acid (10.0 g, 37.78 mmol) in CH2Cl2 (150 mL) was added oxalyl chloride (9.90 mL, 113.6 mmol) and DMF (0.15 mL). The mixture was stirred for 2 h at room temperature, concentrated in vacuo, and re-dissolved into 100 mL of acetone. The obtained acyl chloride solution was added portionwise to another flask containing NaN3 (12.31 g, 190 mmol) in H2O (100 mL) at 0° C. After 10 min, The reaction mixture was diluted with brine (300 mL) and extracted with EtOAc (500 mL). The organic layer was separated, dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained acyl azide was diluted in 150 mL of toluene and heated at 95° C. until no more gas evolution occurred (approx. 1.5 h). The reaction mixture was cooled to rt and treated with 100 mL of dioxane and 300 mL of 1 M aqueous HCl. The resulting two-phase solution was heated to 95° C. After approx. 2.5 h, the reaction mixture was cooled to rt, made basic with dilute NH4OH, and extracted with EtOAc (500 ml). The organic layer was separated, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by flash chromatography (SiO2, 0-100% EtOAc/CH2Cl2 gradient elution) to yield 1-(4-chlorophenyl)-5-isopropylpyrazol-4-amine (5.7 g, 64%).

1. concentrationconcentrated in vacuo
2. dissolutionre-dissolved into 100 mL of acetone
3. additionThe obtained acyl chloride solution was added portionwise to another flask
4. waitAfter 10 min
5. extractionextracted with EtOAc (500 mL)
6. customThe organic layer was separated
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated in vacuo
9. additionThe obtained acyl azide was diluted in 150 mL of toluene
10. temperatureheated at 95° C. until no more gas evolution
11. custom(approx. 1.5 h)
12. temperatureThe reaction mixture was cooled to rt
13. additiontreated with 100 mL of dioxane and 300 mL of 1 M aqueous HCl
14. temperatureThe resulting two-phase solution was heated to 95° C
15. waitAfter approx. 2.5 h
16. temperaturethe reaction mixture was cooled to rt
17. extractionextracted with EtOAc (500 ml)
18. customThe organic layer was separated
19. dry with materialdried over anhydrous sodium sulfate
20. concentrationconcentrated in vacuo
21. custompurified by flash chromatography (SiO2, 0-100% EtOAc/CH2Cl2 gradient elution)

ORD-Eintrag

ord-318712f4391045a3964dd72316122540

Quelldatensatz

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09169248B2