Benzaldehyde → Trifluoroacetic acid

Participants

Reaction Conditions

Reaction Steps

To a suspension of 3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-amine trifluoroacetate salt (0.094 g, 0.22 mmol) in toluene (3 mL) and ethanol (1 mL) was added Hunig's Base (0.11 mL, 0.66 mmol). The mixture was vortexed to ensure dissolution followed by the addition of benzaldehyde (22 μL, 0.22 mmol). The reaction mixture was heated at 100° C. for 2 hours followed by removal of solvent under reduced pressure. To the residue was added dichloromethane (10 mL), Hunig's Base (0.10 mL) followed by sodium triacetoxyborohydride (0.173 g, 0.66 mmol). The reaction mixture was shaken at room temperature for 65 hours. The reaction was quenched by addition of 1.5M NaOH (10 mL) and shaking it at room temperature for 1 hour. The organic layer was then separated, washed with brine (2×10 mL) and concentrated under reduced pressure to give the crude product. The crude product was purified by reverse phase HPLC to give the desired product, N-benzyl-3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-amine as a TFA salt and a pale yellow solid (0.045 g, 51%). Alternatively the crude product could be used in the next step without any further purification M.p.>178° C.; 400 MHz 1H NMR (DMSO-d6) δ: 9.07 (brs, 2H), 8.08 (s, 1H), 8.02 (s, 1H), 7.56-7.44 (m, 5H), 7.16 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 5.54 (s, 2H), 4.32 (t, J=6.0 Hz, 2H), 3.69 (s, 3H), 3.64 (m, 1H), 3.41 (m, 1H), 3.11 (m, 3H), 2.41 (m, 1H), 1.98 (m, 1H); LCMS [M+H]: 399.

Provenance & Evidence