2-Aminopyridine → 2-(8-Chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid pyridin-2-ylamide

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Reaction Steps

A solution of (S)-2-[(5-chloro-2-formyl-4H-chromen-3-ylmethyl)-methyl-amino]-4-methyl-pentanoic acid (300 mg, 2.1 mmol), commercially available 2-aminopyridine (101 mg, 1.07 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (190 mg, 0.98 mmol), and N-hydroxybenzotriazole (HOBt) (132 mg, 0.982 mmol) in methylene chloride (15 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 gradiant elution, to afford S)-2-(8-Chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid pyridin-2-ylamide (970 mg, 26.4%), as a white solid. 1H NMR (DMSO-d6) δ: 10.89 (s, 1H), 8.34 (d, J=3.9 Hz, 1H), 8.01 (d, J=7.8 Hz, 1H), 7.77 (t, J=7.3 Hz, 1H), 7.21-7.42 (m, 2H), 7.02-7.17 (m, 2H), 5.07 (d, J=4.9 Hz, 1H), 4.44 (d, J=18.6 Hz, 1H), 4.07 (d, J=18.6 Hz, 1H), 3.75 (s, 2H), 1.75-1.90 (m, 1H), 1.61-1.74 (m, 1H), 1.46 (br. s., 1H), 1.24 (s, 1H), 0.93 (t, J=5.9 Hz, 6H).

Provenance & Evidence