Sodium Carbonate → 6-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-4'-fluorobiphenyl-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-bromo-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile (0.100 g, 0.347 mmol) and 4-fluorophenylboronic acid (0.158 g, 1.04 mmol) in DME (2 mL), aqueous solutions of Na2CO3 (0.69 mL, 2 M) and KOH (0.17 mL, 2 M) are added. After degassing with nitrogen, Pd(PPh3)4 (0.040 g, 0.035 mmol) is added. Mixture is heated in a microwave reactor at 130° C., for 20 minutes. LCMS showed consumption of starting material. The solution is then diluted with ethyl acetate and saturated aqueous sodium bicarbonate. The resulting aqueous layer is extracted further with ethyl acetate (3×). The combined organic layers are washed with brine and dried over anhydrous sodium sulfate. After concentration, crude product is purified by flash chromatography (Hexane/EtOAc, and then 10% MeOH/DCM) followed by preparative HPLC (0-50% acetonitrile with 0.1% TEA in 21 minutes). After concentration and free basing, 6-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-4′-fluorobiphenyl-3-carbonitrile is obtained as a white powder. MS (ESI) m/z 304.0 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.38-2.54 (m, 1H), 2.76-3.03 (m, 3H), 5.33 (app t, J=6.7 Hz, 1H), 6.79 (s, 1H), 7.01 (d, J=8.1 Hz, 1H), 7.15-7.24 (m, 3H), 7.29 (dd, J=13.4, 5.1 Hz, 2H), 7.54-7.65 (m, 2H).

Provenance & Evidence