4-Hydroxybenzaldehyde → HCID 178486397, compound

Participants

Reaction Conditions

Reaction Steps

2-[3,4-bis(methyloxy)phenyl]4,4,4-trifluoro-3-oxobutanenitrile (100 mg, 0.37 mmol) was dissolved in benzene (10 mL), acetic acid (1 mL), and anhydrous hydrazine (98%, 12 μL, 0.44 mmol). The resulting mixture was heated at reflux for 3 hours. It was cooled, concentrated, and the residue was basified with solid sodium bicarbonate, diluted with ethyl acetate (50 mL), washed with water and brine (50 mL each), dried over sodium sulfate, filtered, concentrated, and the residue was dried in vacuum to give an oily residue. To this residue was added of 4-hydroxybenzaldehyde (67 mg, 0.55 mmol) and trifluoroacetic acid (1 mL), and the mixture was heated at 70° C. for 18 hours. Then the reaction mixture was concentrated, dissolved in 10 mL of N,N-dimethylformamide and purified by preparatory HPLC (Shimadzu LC-8A HPLC, Waters Xterra C18 30 mm×100 mm column, acetonitrile-water-trifluoroacetic eluent). After concentration then then lyophillization of the pure fractions 4-[7,8-bis(methyloxy)-1-(trifluoromethyl)-3H-pyrazolo[3,4-c]isoquinolin-5-yl]phenol trifluoroacetic acid salt (56 mg, 0.11 mmol, 30% yield) was obtained. 1H NMR (400 MHz, d6-DMSO): 7.63-7.61 (d, 2H), 7.59 (s, 1H), 7.58 (s, 1H), 6.99-6.97 (d, 2H), 4.00 (s, 3H), 3.80 (s, 3H); MS (EI) for C19H14N3O3F3: 340 (MH+).

Provenance & Evidence