Hydrochloric Acid → 3-(Tetrahydro-2H-pyran-4-yl)-1-p-tolyl-1H-pyrazol-5-amine

To a mixture of acetonitrile (500 μL, 390 mg, 9.60 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 methyl tetrahydro-2H-pyran-4-carboxylate (5.1 mL, 5.5 g, 38 mmol) and the reaction mixture maintained at RT for 16 hr. The resulting mixture was concentrated in vacuo to a volume of ˜20 mL, was diluted with EtOH (20 mL) and treated with p-tolylhydrazine hydrochloride (1.52 g, 9.57 mmol) and was acidified to pH 1 by the addition of conc hydrochloric acid. 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 residue was diluted with water (30 mL), adjusted to pH 12 by the addition of 2M aq NaOH and the mixture extracted with EtOAc (2×20 mL). The combined extracts were washed with brine (30 mL) and then dried and evaporated in vacuo. The residue was triturated with isohexane to afford the title compound, Intermediate A31, as a pale brown solid (1.94 g, 78%); Rt 1.28 min (Method 2); m/z 258 (M+H)+, (ES+).

1. concentrationThe resulting mixture was concentrated in vacuo to a volume of ˜20 mL
2. additionwas diluted with EtOH (20 mL)
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 residue was diluted with water (30 mL)
7. additionadjusted to pH 12 by the addition of 2M aq NaOH
8. extractionthe mixture extracted with EtOAc (2×20 mL)
9. washThe combined extracts were washed with brine (30 mL)
10. customdried
11. customevaporated in vacuo
12. customThe residue was triturated with isohexane

ORD record

ord-e5fbfc798e9a4f0cbde7593da40f5d02

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09024041B2