Hydrochloric Acid → 3-Oxo-3-(5,6,7,8-tetrahydronaphthalen-2-yl)propanenitrile

Acetonitrile (21.48 mL, 411 mmol) was added to a stirred suspension of 60% NaH (7.05 g, 176 mmol) in dioxane (200 mL) and the resulting mixture was stirred at rt for 20 min. Solution of ethyl 5,6,7,8-tetrahydronaphthalene-2-carboxylate (12 g, 58.7 mmol) in dioxane (50 mL) was then added and the mixture was heated at reflux for 4 h. After cooling to rt, water followed by 1N HCl (100 mL) was added and the mixture was extracted twice with dichloromethane, dried (Na2SO4), filtered and concentrated to afford 3-oxo-3-(5,6,7,8-tetrahydronaphthalen-2-yl)propanenitrile as dark solid. A mixture of this syrup and hydrazine hydrate (2.77 mL, 88 mmol) in ethanol (200 mL) was refluxed for 16 h. The reaction mixture was then cooled to rt and concentrated in vacuo. The resulting crude was diluted with dichloromethane and washed with water, dried (Na2SO4), filtered, concentrated and purified by silica gel chromatography (5-10% CH2Cl2/MeOH) to afford desired 3-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-5-amine (6.1 g, 28.6 mmol, 48.7% yield) as yellow solid. 1H NMR (400 MHz, CDCl3) δ: 7.26 (d, J=3.5 Hz, 2H), 7.12 (d, J=7.8 Hz, 1H), 5.89 (s, 1H), 4.14 (br. s., 3H), 2.88-2.75 (m, 4H), 1.83 (dt, J=6.1, 3.4 Hz, 4H). LCMS (M+H)=214.2.

1. temperaturethe mixture was heated
2. temperatureat reflux for 4 h
3. temperatureAfter cooling to rt
4. additionwas added
5. extractionthe mixture was extracted twice with dichloromethane
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-1921a2ea1d564483840cafc187960f1f

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08633200B2