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 room temp 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 room temp, 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 heated at reflux for 16 h. The reaction mixture was cooled to room temp and concentrated in vacuo. The residue was diluted with dichloromethane and washed with water, dried (Na2SO4), filtered, concentrated and purified by silica gel chromatography (5-10% MeOH/CH2Cl2) 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 room temp
4. additionwas added
5. extractionthe mixture was extracted twice with dichloromethane
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-6c84e6df6709420aa30cf45fa7087761

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034882B2