Dimethylformamide → Ammonium Hydroxide

Participants

Reaction Steps

A flask is charged with 3-methyl-2-pyridin-3-yl-1H-indole hydrochloride (Example 1, 0.080 g, 0.326 mmol) and DMF (1.5 mL), and 60% NaH in mineral oil (0.028 g, 0.719 mmol) is added. The mixture is stirred at room temperature for 20 min, followed by addition of 4-bromomethyl-3-fluoro-benzonitrile (0.175 g, 0.817 mmol). The reaction mixture stirred at room temperature for 30 min. The residue is diluted with DMF (1.5 mL), filtered and purified by reverse phase HPLC with Xbridge Shield RP18 column and a 0.1% aqueous NH4OH in acetonitrile gradient to afford 3-fluoro-4-(3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzonitrile as a yellow solid. 1H NMR (400 MHz, MeOD) δ ppm 2.32 (s, 3H), 5.47 (s, 2H), 6.62 (t, J=7.6 Hz, 1H), 7.20 (t, J=7.5 Hz, 1H), 7.27 (t, J=7.6 Hz, 1H), 7.38 (d, J=8.1 Hz, 2H), 7.50 (d, J=9.9 Hz, 1H), 7.56 (dd, J=7.8, 4.8 Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 7.86 (dd, J=7.8, 1.8 Hz, 1H), 8.52 (s, 1H), 8.60 (dd, J=4.9, 1.6 Hz, 1H). HRMS (ESI) m/z 342.1394 [(M+H)+ Calcd for C22H17FN3: 342.1407].

Provenance & Evidence