反应详情

A solution of (S)-2-[(5-chloro-2-formyl-4H-chromen-3-ylmethyl)-methyl-amino]-4-methyl-pentanoic acid (300 mg, 2.1 mmol) (Example 3, Step 1), commercially available 6-amino-nicotinic acid methyl ester (163 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 gradient elution, afforded 6-[(S)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoylamino]-nicotinic acid methyl ester (143 mg, 3%), as a white solid. 1H NMR (DMSO-d6) δ: 11.36 (s, 1H), 8.87 (s, 1H), 8.29 (dd, J=8.8, 2.0 Hz, 1H), 8.15 (d, J=8.8 Hz, 1H), 7.18-7.39 (m, 2H), 7.09 (dd, J=6.8, 2.0 Hz, 1H), 5.09 (dd, J=10.8, 4.4 Hz, 1H), 4.43 (d, J=19.1 Hz, 1H), 4.08 (d, J=19.1 Hz, 1H), 3.86 (s, 3H), 3.75 (s, 2H), 1.78-1.92 (m, 1H), 1.63-1.76 (m, 1H), 1.47 (br. s., 1H), 0.93 (t, J=5.9 Hz, 6H).

1. extractionextracted with ethyl acetate (3×)
2. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
3. concentrationconcentrated in vacuo
4. washhexane-ethyl acetate gradient elution