Hydrochloric Acid → 3-Cyclopropyl-1-p-tolyl-1H-pyrazol-5-amine

To a solution of acetonitrile (500 μL, 390 mg, 9.6 mmol) in THF (30 mL) at RT was added a solution of potassium 2-methylbutan-2-olate in toluene (1.7 M, 17.0 mL, 29.0 mmol) followed by the dropwise addition of ethyl cyclopropanecarboxylate (4.56 mL, 4.37 g, 38.0 mmol) and the reaction mixture maintained at RT for 16 hr. The resulting mixture was concentrated in vacuo to a volume of ˜15 mL and was then diluted with EtOH (20 mL) and p-tolylhydrazine hydrochloride (1.52 g, 9.57 mmol) was added. The mixture was acidified to pH 1 by the addition of conc hydrochloric acid and the resulting heterogeneous mixture was heated to 70° C. for 2 hr, then cooled to RT and concentrated in vacuo to a volume of ˜20 mL. The mixture was diluted with water (30 mL) and was adjusted to pH 12 by the addition of 2M aq NaOH and extracted with diethyl ether (2×20 mL). The combined organic extracts were washed with brine (30 mL) and then dried and evaporated in vacuo. The residue was triturated with isohexane (20 mL) to afford the title compound, Intermediate A28, as a beige solid (1.60 g, 77%); Rt 3.35 min (Method 1 basic); m/z 214 (M+H)+, (ES+).

1. concentrationThe resulting mixture was concentrated in vacuo to a volume of ˜15 mL
2. additionwas added
3. temperaturethe resulting heterogeneous mixture was heated to 70° C. for 2 hr
4. temperaturecooled to RT
5. concentrationconcentrated in vacuo to a volume of ˜20 mL
6. additionThe mixture was diluted with water (30 mL)
7. additionwas adjusted to pH 12 by the addition of 2M aq NaOH
8. extractionextracted with diethyl ether (2×20 mL)
9. washThe combined organic extracts were washed with brine (30 mL)
10. customdried
11. customevaporated in vacuo
12. customThe residue was triturated with isohexane (20 mL)

ORD record

ord-85266e49190146d496becc5a41d4fda0

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09024041B2