p-Toluenesulfonic acid → HCID 86722463, compound

Participants

Reaction Conditions

Reaction Steps

A flask was charged with 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carbaldehyde (111, R1=4-Fluorophenyl) (58.15 g, 283 mmol, cyclohexane-1,3-dione (47.7 g, 425 mmol) and toluene (600 mL). The slurry was stirred then pTSA (4.8 g, 25.2 mmol) was added. The mixture was warmed in an oil bath heated to about 100° C. for about 1 h. The mixture was allowed to cool to rt and stir overnight. The mixture was concentrated to dryness under reduced pressure. Water (400 mL), sat. aq. NaHCO3 (50 mL) and ethanol (100 mL) were added to the mixture. The supernatant was decanted and the solids were triturated with water (100 mL). The supernatant was decanted and the process repeated with another portion of water (100 mL). The solids were dried under reduced pressure to remove residual water. The material was stirred with MeOH (160 mL) then the solids were collected by filtration and washed with MeOH (80 mL). The material was dried under vacuum at about 65° C. to yield 1-(4-fluorophenyl)-7,8-dihydro-1H-pyrazolo[3,4-b]quinolin-5(6H)-one (112, R1=4-Fluorophenyl) (55.5 g, 70%); LC/MS, method 3, Rt=2.37 min, MS m/z 282 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.82 (s, 1H), 8.56 (s, 1H), 8.32-8.23 (m, 2H), 7.51-7.39 (m, 2H), 3.22 (t, J=6.2 Hz, 2H), 2.76-2.69 (t, J=6.0 Hz, 2H), 2.20-2.11 (m, 2H).

Provenance & Evidence