3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine → HCID 59490542, compound

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Reaction Steps

Step-1: Synthesis of ethyl 3-(6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7-carboxamido)benzoate. Step (i): A solution of 3-(4-methoxy-benzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine (0.945 g, 3.21 mmol) in trifluoroacetic acid (10 mL) was heated at 65° C. for 16 hours. Once the reaction was complete the solvent was removed under reduced pressure to give a dark brown solid. The product was used in the next step without any further purification. Step (ii): To the dark brown solid was added dichloromethane (30 mL) and Hunig's Base (5 mL). The mixture was vortexed to ensure that the solid had dissolved, then cooled in an ice-bath followed by the addition of 3-isocyanato-benzoic acid ethyl ester (0.613 g) as a solution in anhydrous dichloromethane (10 mL) in a drop wise fashion. The reaction was then shaken at room temperature for 20 minutes. Once the reaction was complete water (20 mL) was added and the reaction mixture was then extracted with CH2Cl2 (60 mL). The organic extract was washed with brine (2×20 mL), dried using sodium sulfate, filtered and concentrated to give desired crude product. The crude product was then purified using flash column chromatography (SiO2, 80% EtOAc in hexanes) to give the pure desired product, ethyl 3-(6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7-carboxamido)benzoate (0.98 g, 83%) as a white solid. M.p. 184-186° C.; 1H NMR (400 MHz, DMSO-d6) δ13.59 (s, 1H), 8.97 (s, 1H), 8.35 (s, 1H), 8.17 (s, 1H), 8.13 (t, J=1.6 Hz, 1H), 7.83 (m, 1H), 7.56 (m, 1H), 7.39 (dd, J1=J2=8.0 Hz, 1H), 4.80 (s, 2H), 4.30 (q, J=6.8 Hz, 2H), 3.86 (t, J=6.0 Hz, 2H), 3.15 (t, J=5.6 Hz, 2H), 1.32 (t, J=6.8 Hz, 3H); LCMS [M+H]: 366.

Provenance & Evidence