反应详情

To a mixture of 6-chloro-3-iodo-chromone (1A, 30.65 g, 0.1 mol), 4-ethynylaniline (14.05 g, 0.12 mol), PdCl2(PPh3)2 (1.404 g, 2.0 mmol) and CuI (190 mg, 1.0 mmol) was added anhydrous CH3CN (500 mL). Upon stirring, diisopropylethylamine (DIPEA, 69.7 mL, 0.4 mol) was added slowly to the above mixture. The reaction mixture was stirred at rt for 5 h. LCMS indicated all of 1A was consumed. 2-Hydroxyethylhydrazine (22 mL, 0.325 mol) was then added. The mixture was stirred at rt overnight. The mixture was filtered and the solid was washed with small amount of CH3CN, and dried under high vacuum to give 2A (8.1 g). Silica (˜100 mL) was added to the filtrate, and the solvent was removed with rotavapor. The resultant powder was load on a silica column and eluted with hexanes-ethyl acetate (v/v 2/1, 2/3, 1/1, 1/2) and then pure ethyl acetate. The fractions containing 2A were combined and solvent was removed. The residua were recrystallized from hexanes-ethyl acetate to give 2A (16.5 g). Total 24.6 g of the title compound 2A was obtained, and the yield is 69.5%. 1H NMR (CDCl3/CD3OD=5/1, 500 MHz) δ 8.71 (d, 1H, J=1.5 Hz), 7.80 (s, 1H), 7.39 (d, 2H, J=7.5 Hz), 7.19 (dd, 1H, J=8.0, 1.5 Hz), 6.95 (d, 1H, J=8.5 Hz), 6.70 (d, 2H, J=7.5 Hz), 4.28 (t, 2H, J=5.0 Hz), 3.98 (t, 2H, J=5.0 Hz). LCMS (ESI) m/z 354.17 (MH+, 100); HPLC: tR=4.05 min.

1. stirringThe reaction mixture was stirred at rt for 5 h
2. customwas consumed
3. stirringThe mixture was stirred at rt overnight
4. filtrationThe mixture was filtered
5. washthe solid was washed with small amount of CH3CN
6. customdried under high vacuum