Thionyl Chloride → HCID 59743132, compound

Participants

Reaction Steps

A mixture of 1-chloro-4-oxo-3,4-dihydro-phthalazine-6-carboxylic acid and 4-chloro-1-oxo-1,2-dihydro-phthalazine-6-carboxylic acid (311 mg, 1.385 mmol), catalytic DMF and thionyl chloride (7 mL) was refluxed for 3 hours. The solution was cooled, concentrated under vacuum and treated 3 times with toluene in order to remove the excess thionyl chloride. The crude residue was dissolved in DMF (3 mL) and added dropwise to a 0° C. solution of 3-(trifluoromethyl)benzylamine (0.22 mL, 1.524 mmol), DMF (5 mL) and 60% NaH (199 mg, 8.31 mmol). The reaction was stirred at room temperature overnight, diluted with water and extracted with EtOAc (×3). The combined organic layers were washed with water, brine and dried (Na2SO4). Column chromatography (Hex/EtOAc) afforded 1-chloro-4-oxo-3,4-dihydro-phthalazine-6-carboxylic acid 3-trifluoromethyl-benzylamide (30 mg) as a white solid. 1H NMR (400 MHz, d6-DMSO) δ: 4.62 (d, 2H), 7.65 (m, 4H), 8.10 (d, 1H), 8.47 (dd, 1H), 8.80 (d, 1H), 9.65 (t, 1H), 12.99 (s, 1H) ppm; m/z (M+1) 382.17; and 4-chloro-1-oxo-1,2-dihydro-phthalazine-6-carboxylic acid 3-trifluoromethyl-benzylamide (33 mg) as a white solid.

Provenance & Evidence