Dichloromethane → N-(1-acetyl-1H-pyrazol-4-yl)acetamide

Temperature

5 °C

A 250-mL 3-neck flask was charged with 1H-pyrazol-4-amine (5 g, 60.2 mmol) and dichloromethane (50 mL). The resulting suspension was cooled to 5° C. and triethylamine (TEA, 9.13 g, 90.0 mmol) was added, followed by acetic anhydride (Ac2O, 7.37 g, 72.2 mmol) at <20° C. The reaction was stirred at room temperature for 18 h, at which point thin layer chromatography [Eluent: ethyl acetate] analysis indicated that the reaction was incomplete. Additional triethylamine (4.57 g, 45.0 mmol) and acetic anhydride (3.70 g, 36.0 mmol) were added and the reaction was heated at 30° C. for an additional 3 hours to give a dark solution, at which point thin layer chromatography analysis indicated that only a trace of starting material remained. The reaction mixture was purified by flash column chromatography using ethyl acetate as eluent. The fractions containing pure product were combined and concentrated to dryness to afford an off-white solid. The solid was dried under vacuum at room temperature for 18 hours (5.55 g, 55%): 1H NMR (400 MHz, DMSO-d6) δ 10.30 (s, 1H), 8.39 (d, J=0.7 Hz, 1H), 7.83 (d, J=0.7 Hz, 1H), 2.60 (s, 3H), 2.03 (s, 3H); EIMS m/z 167 ([M]+).

1. temperaturethe reaction was heated at 30° C. for an additional 3 hours
2. customto give a dark solution
3. customThe reaction mixture was purified by flash column chromatography
4. additionThe fractions containing pure product
5. concentrationconcentrated to dryness
6. customto afford an off-white solid
7. customThe solid was dried under vacuum at room temperature for 18 hours (5.55 g, 55%)

ORD record

ord-8587827c95d34a3db96a2a6b1bc695e6

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09044017B2