4-Methylmorpholine → HCID 54767966, 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 (Example 13, step 2c) (100 mg, 0.24 mmol), in tetrahydrofuran (10 mL) was treated with N-methylmorpholine (100 mg, 0.74 mmol), 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HATU) (284 mg, 0.74 mmol) and commercially available 2-amino-5-chloropyridine (38 mg, 0.29 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)—N-(5-chloro-pyridin-2-yl)-3-cyclohexyl-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide (31 mg, 24.4%), as a white solid. 1H NMR (DMSO-d6) δ: 11.05 (br. s., 1H), 8.39 (br. s., 1H), 8.04 (d, J=8.3 Hz, 1H), 7.89 (d, J=8.8 Hz, 1H), 6.91 (d, J=8.8 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 5.08 (d, J=5.9 Hz, 1H), 4.37 (d, J=19.1 Hz, 1H), 4.02 (d, J=18.6 Hz, 1H), 3.76 (s, 6H), 3.55 (br. s., 2H), 1.53-1.85 (m, 7H), 0.75-1.29 (m, 6H).

Provenance & Evidence