Oxalyl chloride → (S)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (5-chloro-pyridin-2-yl)-amide

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-propionic acid (200 mg, 2.1 mmol) (from Example 3, Step 1c), in methylene chloride (10 mL) was treated with oxalyl chloride (0.12 mL, 1.07 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 (0.61 mL, 3.57 mmol) and commercially available 5-chloro-pyridin-2-ylamine (137 mg, 1.07 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)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (5-chloro-pyridin-2-yl)-amide (145 mg, 36.3%), as a white solid. 1H NMR (DMSO-d6) δ: 11.11 (s, 1H), 8.40 (d, J=2.4 Hz, 1H), 8.05 (d, J=8.8 Hz, 1H), 7.90 (dd, J=8.8, 2.4 Hz, 1H), 7.21-7.38 (m, 2H), 7.09 (dd, J=7.1, 2.2 Hz, 1H), 5.06 (dd, J=10.5, 4.6 Hz, 1H), 4.42 (d, J=18.6 Hz, 1H), 4.07 (d, J=19.1 Hz, 1H), 3.75 (s, 2H), 1.77-1.89 (m, 1H), 1.61-1.73 (m, 1H), 1.46 (br. s., 1H), 0.93 (t, J=6.4 Hz, 6H).

Provenance & Evidence