Sodium Carbonate → HCID 118045198, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of (S)-4-bromo-2-fluoro-N-(2-hydroxy-1-phenylethyl)benzamide (67.1 mg, 0.20 mmol) in DME (5 mL) was added tert-butyl 4-(6-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidine-1-carboxylate (40 mg, 0.099 mmol) and sodium carbonate (0.24 mL, 0.49 mmol). The mixture was purged with nitrogen for 10 min, then PdCl2(dppf)-CH2Cl2Adduct (12.15 mg, 0.015 mmol) was added. The reaction mixture was heated to 120° C. in an oil bath for 3 h. The reaction mixture was diluted with ethyl acetate. The organic solution was washed with water, brine, dried over sodium sulfate and concentrated. The resulting residue was treated with 30% TFA in DCM (20 mL) for 15 min. The reaction mixture was concentrated and the crude product was purified by HPLC to give (S)-4-(2-amino-5-(piperidin-4-yl)pyridin-3-yl)-2-fluoro-N-(2-hydroxy-1-phenylethyl)benzamide (9 mg, 20.8%) as TFA salt. LCMS (m/z): 435 (MH+), 0.44 min; 1H NMR (300 MHz, CD3OD) δ ppm 8.63 (br. s., 1H) 7.90 (t, J=7.77 Hz, 1H) 7.84 (s, 2H) 7.47-7.24 (m, 7H), 5.27-5.17 (m, 1H) 3.93-3.79 (m, 2H) 3.52 (d, J=12.60 Hz, 2H) 3.21-3.05 (m, 2H) 2.96 (t, J=12.31 Hz, 1H) 2.15 (d, J=14.07 Hz, 2H) 1.96-1.78 (m, 2H).

Provenance & Evidence