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 1c), commercially available 2-aminothiazole (109 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 (S)-2-(8-chloro-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid thiazol-2-yl-amide (200 mg, 53%), as a light yellow solid. 1H NMR (DMSO-d6) δ: 12.58 (br. s., 1H), 7.50 (d, J=3.4 Hz, 1H), 7.19-7.36 (m, 3H), 7.09 (dd, J=7.1, 2.2 Hz, 1H), 5.05 (dd, J=10.8, 4.9 Hz, 1H), 4.40 (d, J=19.1 Hz, 1H), 4.09 (d, J=18.6 Hz, 1H), 3.76 (br. s., 2H), 1.78-1.92 (m, 1H), 1.63-1.76 (m, 1H), 1.46 (br. s., 1H), 0.93 (t, J=7.1 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