Hydrochloric Acid → 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine

Temperature

35 °C

Alternate synthetic route to 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-amine (2-10): To a 3-neck, 100-mL round bottom flask was charged N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide (5 g, 21.13 mmol) and tetrahydrofuran (50 mL). Sodium tert-butoxide (4.06 g, 42.3 mmol) was added (causing a temperature rise from 22° C. to 27.6° C.), followed by ethyl bromide (6.26 mL, 85 mmol). The reaction was stirred at 35° C. for 144 h at which point only 3.2% (AUC) starting material remained. The reaction mixture was concentrated to give a brown residue, which was dissolved in 1 N hydrochloric acid (106 mL, 106 mmol) and heated at 80° C. for 24 hours, at which point HPLC analysis indicated that the starting material had been consumed. The reaction was cooled to 20° C. and basified with sodium hydroxide (50 wt % in water) to pH>9. The resulting suspension was stirred at 20° C. for 1 hour and filtered. The filter cake was rinsed with water (25 mL) to afford a brown solid (5.18 g). The resulting crude product was dissolved in ethyl acetate and passed through a silica gel plug (50 g) using ethyl acetate (500 mL) as eluent. The filtrate was concentrated to dryness to afford a white solid (3.8 g, 80%).

1. customfrom 22° C. to 27.6° C.
2. concentrationThe reaction mixture was concentrated
3. customto give a brown residue, which
4. temperatureheated at 80° C. for 24 hours, at which point HPLC analysis
5. customhad been consumed
6. temperatureThe reaction was cooled to 20° C.
7. stirringThe resulting suspension was stirred at 20° C. for 1 hour
8. filtrationfiltered
9. washThe filter cake was rinsed with water (25 mL)

ORD record

ord-444f76520e924ed8a121058fbefc7495

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156813B1