4-Methylmorpholine → HCID 54767968, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (100 mg, 0.24 mmol), in tetrahydrofuran (10 mL) was treated with N-methylmorpholine (760 mg, 0.69 mmol), 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HATU) (263 mg, 0.69 mmol) and commercially available 2-amino-5-chloropyridine (42 mg, 0.33 mmol). The mixture was heated in a sealed tube was heated for 16 hours at 90° C. The reaction mixture was diluted with water and extracted with ethyl acetate (3×). 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 gradient elution, afforded (S)-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (5-chloro-pyridin-2-yl)-amide (21 mg, 16.2%), as an off white solid. 1H NMR (DMSO-d6) δ: 11.09 (br. s., 1H), 8.40 (br. s., 1H), 8.05 (d, J=8.8 Hz, 1H), 7.90 (d, J=8.8 Hz, 1H), 6.91 (d, J=8.8 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 5.05 (br. s., 1H), 4.38 (d, J=19.1 Hz, 1H), 4.03 (d, J=18.6 Hz, 1H), 3.76 (s, 6H), 3.55 (br. s., 2H), 1.82 (br. s., 1H), 1.67 (br. s., 1H), 1.45 (br. s., 1H), 0.93 (t, J=6.1 Hz, 6H).

Provenance & Evidence