Sodium Carbonate → HCID 58827084, compound

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) given in Example 3 (table 2) and trimethylboroxine (0.145 g, 1.04 mmol) in DME (3 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. The mixture is heated in a microwave reactor at 130° C. 1.5 h. At that point LCMS showed consumption of the starting material. The solution is diluted with ethyl acetate and saturated 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 the crude product is filtered through 0.45 μm filter and then purified by preparative HPLC (0% for 5 minutes and 0-34% acetonitrile with 0.1% TFA in 17 minutes). MS (ESI) m/z 224.0 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.33-2.42 (m, 1H), 2.43 (s, 3H), 2.84-2.95 (m, 2H), 3.07-3.18 (m, 1H), 5.54 (dd, J=8.1, 4.8 Hz, 1H), 6.65 (d, J=8.1 Hz, 1H), 6.83 (s, 1H), 7.32 (s, 1H), 7.41 (d, J=8:1 Hz, 1H), 7.50 (s, 1H). Resolution of the (R) and (S) enantiomers of the title compound is achieved by chiral HPLC using ChiralPak AS-H column and 9:1 hexane/EtOH to give enantiomer A (tr=84 min) and enantiomer B (tr=104 min).

Provenance & Evidence