2-Aminothiazole → (S)-3-Cyclohexyl-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-N-thiazol-2-yl-propionamide

Participants

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, 0.54 mmol) (Example 7, Step 2c), commercially available 2-amino-thiazole (66 mg, 0.64 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (113 mg, 0.59 mmol), and N-hydroxybenzotriazole (HOBt) (80 mg, 0.59 mmol) in methylene chloride (10 mL) was stirred for 16 hours at 25° 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)-3-Cyclohexyl-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-N-thiazol-2-yl-propionamide (68 mg, 27.9%), as an off white solid. 1H NMR (DMSO-d6) δ: 12.56 (br. s., 1H), 7.49 (d, J=3.4 Hz, 1H), 7.11-7.31 (m, 2H), 6.77 (d, J=7.8 Hz, 1H), 6.68 (d, J=8.3 Hz, 1H), 5.05 (d, J=5.4 Hz, 1H), 4.36 (d, J=19.1 Hz, 1H), 4.05 (d, J=18.6 Hz, 1H), 3.82 (s, 3H), 3.55 (br. s., 2H), 1.47-1.89 (m, 7H), 0.78-1.29 (m, 6H).

Provenance & Evidence