2-Aminopyridine → (S)-3-cyclohexyl-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-N-pyridin-2-yl-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-propionic acid (200 mg, 0.64 mmol), in methylene chloride (10 mL) was treated with oxalyl chloride (0.07 mL, 0.64 mmol) at 0° C. The mixture was warmed to 25° C. and stirred for additional 2 hours. Then, the reaction mixture was cooled to 0° C., and N,N′-diisopropylethyl amine (0.34 mL, 1.92 mmol) and commercially available 2-amino-pyridine (68 mg, 0.64 mmol), were added. The reaction mixture was stirred for 16 hours at 25° C. The reaction mixture was diluted with water and extracted with ethyl acetate (2×). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue, upon silica gel flash chromatography using hexane-ethyl acetate gradiant elution, afforded (S)-3-cyclohexyl-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-N-pyridin-2-yl-propionamide (42 mg, 17.4%), as a white solid. 1H NMR (DMSO-d6) δ: 10.85 (s, 1H), 8.33 (d, J=3.9 Hz, 1H), 8.00 (d, J=8.3 Hz, 1H), 7.77 (t, J=7.3 Hz, 1H), 7.22 (t, J=8.3 Hz, 1H), 7.12 (t, J=5.9 Hz, 1H), 6.77 (d, J=7.8 Hz, 1H), 6.68 (d, J=8.3 Hz, 1H), 5.08 (br. s., 1H), 4.39 (d, J=18.6 Hz, 1H), 4.03 (d, J=19.1 Hz, 1H), 3.82 (s, 3H), 3.55 (s, 2H), 1.49-1.88 (m, 7H), 0.85-1.32 (m, 6H).

Provenance & Evidence