Lithium hydroxide, monohydrate → 3-Chloro-1-(pyridine-3-yl)-1H-pyrazole-5-carboxylic acid hydrochloride

Methyl 3-chloro-1-(pyridin-3-yl)-1H-pyrazole-5-carboxylate (3.83 g, 16.1 mmol) was stirred in dioxane (53.7 mL). The orange suspension was heated until a solution was achieved. Lithium hydroxide hydrate (1.01 g, 24.2 mmol) in water (26.9 mL) was added to afford a darker red solution. The reaction was stirred at room temperature for 1 hours, at which point LCMS showed the corresponding acid to be the major product. The orange mixture was concentrated to dryness and the residue was mixed with 4 N hydrochloric acid in dioxane (100 mL). The suspension was heated to reflux for 1 hour and allowed to cool to room temperature. The resulting suspension was filtered and the filter cake was rinsed with dioxane. The solid was vacuum dried at 50° C. to afford the desire product as a white solid (4.00 g, 91%): mp 244-246° C.; 1H NMR (400 MHz, DMSO-d6) δ 9.00 (dd, J=2.5, 0.7 Hz, 1H), 8.82 (dd, J=5.2, 1.4 Hz, 1H), 8.35 (ddd, J=8.3, 2.4, 1.4 Hz, 1H), 7.85 (ddd, J=8.3, 5.2, 0.7 Hz, 1H), 7.25 (s, 1H); 13C NMR (101 MHz, DMSO-d6) δ 158.71, 146.00, 143.44, 140.36, 137.00, 136.83, 125.19, 111.71; ESIMS m/z 224 ([M+H]+).

1. temperatureThe orange suspension was heated until a solution
2. customto afford a darker red solution
3. concentrationThe orange mixture was concentrated to dryness
4. additionthe residue was mixed with 4 N hydrochloric acid in dioxane (100 mL)
5. temperatureThe suspension was heated
6. temperatureto reflux for 1 hour
7. temperatureto cool to room temperature
8. filtrationThe resulting suspension was filtered
9. washthe filter cake was rinsed with dioxane
10. customdried at 50° C.

ORD record

ord-ba44736ff50745979b43c9ebd3b3a98f

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434712B2