2-Aminothiazole → (S)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid thiazol-2-ylamide

Participants

Reaction Steps

A solution of (S)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (100 mg, 0.30 mmol), commercially available 2-amino-thiazole (37 mg, 0.36 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (66 mg, 0.33 mmol), and N-hydroxybenzotriazole (HOBt) (44 mg, 0.33 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)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid thiazol-2-ylamide (34 mg, 27.2%), as an off white solid. 1H NMR (DMSO-d6) δ: 12.58 (br. s., 1H), 7.50 (d, J=3.4 Hz, 1H), 7.12-7.34 (m, 2H), 6.76 (d, J=7.8 Hz, 1H), 6.68 (d, J=8.3 Hz, 1H), 5.04 (d, J=5.9 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), 1.83 (d, J=9.3 Hz, 1H), 1.68 (br. s., 1H), 1.45 (br. s., 1H), 0.93 (t, J=7.3 Hz, 6H).

Provenance & Evidence