Sodium Bicarbonate → 2-(3-(4-((methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino)-methyl)-1H-1,2,3-triazol-1-yl)propyl)isoindoline-1,3-dione

Participants

Reaction Steps

A solution of 1-(3-(1,3-dioxoisoindolin-2-yl)propyl)-1H-1,2,3-triazole-4-carbaldehyde, 22, (0.24 g, 0.84 mmol), N-methyl-N-(prop-2-ynyl)-5,6,7,8-tetrahydroquinolin-8-amine, 5, (0.17 g, 1.01 mmol), sodium triacetoxyborohydride (0.27 g, 1.26 mmol) and a catalytic amount of acetic acid (2 drops) in 1,2-dichloroethane (10 mL) was warmed to 65° C. and stirred at this temperature for 24 h. The reaction mixture was cooled to room temperature. A saturated aqueous solution of sodium bicarbonate was added. The product was extracted with dichloromethane. The combined organic layers were dried over potassium carbonate, filtered and concentrated. The crude product was purified by silica gel chromatography (0-5% methanol/CH2Cl2) to afford 0.19 g (80% yield) of the desired product, AH: 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J=4.4 Hz, 1H), 7.79-7.76 (m, 2H), 7.71 (s, 1H), 7.68-7.65 (m, 2H), 7.30 (d, J=7.6 Hz, 1H), 7.00 (dd, J=4.8, 8.0 Hz, 1H), 4.32 (dt, J=3.2, 7.2 Hz, 2H), 3.91 (dd, J=6.0, 9.2 Hz, 1H), 3.77-3.66 (m, 4H), 2.82-2.70 (m, 1H), 2.70-2.60 (m, 1H), 2.29 (s, 3H), 2.29-2.23 (m, 2H), 2.12-2.02 (m, 1H), 2.02-1.92 (m, 1H), 1.92-1.80 (m, 1H), 1.70-1.56 (m, 1H); ESI+ MS: m/z (rel intensity) 431.2 (100, [M+H]+).

Provenance & Evidence