4-Hydroxybenzaldehyde → HCID 178486393, compound

Participants

Reaction Steps

A solution of 1,1-dimethylethyl 4-{5-amino-4-[3,4-bis(methyloxy)phenyl]-1H-pyrazol-3-yl}piperidine-1-carboxylate (0.39 g, 0.97 mmol) and 4-hydroxybenzaldehyde (0.12 g, 0.97 mmol) was heated to 72° C. in trifluoroacetic acid (5 mL) for 18 h. The solvent was evaporated under reduced pressure and the residue was purified by reverse phase HPLC (CH3CN/H2O with 0.1% TFA) to give 4-[7,8-bis(methyloxy)-1-piperidin-4-yl-3H-pyrazolo[3,4-c]isoquinolin-5-yl]phenol trifluoroacetate (0.24 g, 61%). 53 mg (0.12 mmol) 4-[7,8-bis(methyloxy)-1-piperidin-4-yl-3H-pyrazolo[3,4-c]isoquinolin-5-yl]phenol trifluoroacetate was dissolved in ethanol (10 mL) and it was treated with polymer bound Hunig's base (Argonaut Technologies Inc. PS-DIEA, 3.44 mmol/g) for 30 minutes to adjust the pH to 7. The resin was filtered off and the filtrate was concentrated to dryness. The residue was treated with hydrogen chloride (4M in 1,4-dioxane, 3.0 mL). The precipitating solid was collected by filtration to result in 4-[7,8-bis(methyloxy)-1-piperidin-4-yl-3H-pyrazolo[3,4-c]isoquinolin-5-yl]phenol hydrochloride (42 mg, 89%). 1H-NMR (400 MHz, d6-DMSO): 9.18 (s, 1H), 8.78 (s, 1H), 7.48 (d, 2H), 7.44 (d, 2H), 6.88 (d, 2H), 4.00, 3.68 (2 s, 2×3H), 3.34 (m, 2H), 3.16 (m, 2H), 2.22 (m, 2H), 2.02 (m, 2H), 1.22 (m, 1H), MS (EI) for C23H24N4O3: 405.1 (MH+).

Provenance & Evidence