1-Hydroxybenzotriazole → HCID 54765571, compound

Participants

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) (200 mg, 0.55 mmol), commercially available 6-aminonicotinic acid methyl ester (116 mg, 0.66 mmol), N-ethyl-N-dimethyaminopropyl carbodiimide hydrochloride (EDCI. HCl) (116 mg, 0.60 mmol), and N-hydroxybenzotriazole (HOBt) (82 mg, 0.60 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 6-[(S)-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoylamino]-nicotinic acid methyl ester (41 mg, 30.8%), as a white solid. 1H NMR (DMSO-d6) δ: 11.35 (s, 1H), 8.88 (br. s., 1H), 8.28 (d, J=6.8 Hz, 1H), 8.15 (d, J=8.8 Hz, 1H), 6.91 (d, J=8.8 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 5.09 (d, J=5.9 Hz, 1H), 4.41 (s, 1H), 4.36 (br. s., 1H), 4.04 (d, J=18.6 Hz, 1H), 3.86 (s, 3H), 3.76 (s, 6H), 3.55 (br. s., 2H), 1.76-1.94 (m, 1H), 1.61-1.74 (m, 1H), 1.46 (br. s., 1H), 0.93 (t, J=5.9 Hz, 6H).

Provenance & Evidence