Reaction Steps
To a mixture of crude material containing 24 (2.00 g, 5.88 mmol) and 3,5-dichloro-2-hydroxybenzaldehyde (0.011 g, 0.059 mmol) in isopropyl acetate (15.0 ml) at 55-60° C. under nitrogen was slowly added a solution of 1H-indole-2-carboxylic acid (0.96 g, 5.88 mmol) in THF (10.0 ml) over 2 hours. Upon completion of acid addition, a thick salt suspension was agitated at 55-60° C. for another 18 h and then was allowed to cool to ambient temperature. The salt was filtered and washed with isopropyl acetate. After drying at 60° C. in a vacuum oven with nitrogen purge for 8 h, 26 (2.33 g, 79.0%) was isolated as crystals. 1H NMR (500 MHz, DMSO): δ 11.40 (s, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.45 (br, 3H), 7.47 (ddd, J=14.8, 10.1, 8.3 Hz, 1H), 7.41-7.40 (m, 1H), 7.16-7.14 (m, 2H), 6.98-6.97 (m, 1H), 6.87 (s, 1H), 4.69 (dq, J=15.3, 9.6 Hz, 1H), 3.84-3.81 (m, 4H), 2.76-2.71 (m, 1H), 2.34 (dd, J=12.7, 6.3 Hz, 1H), 1.13 (d, J=6.5 Hz, 3H); 13C NMR (100 MHz, DMSO-d6): δ 170.9, 164.8, 156.8 (ddd, J=244, 7.0, 2.5 Hz), 149.1 (ddd, J=249, 14.4, 8.5 Hz), 147.2 (ddd, J=246, 13.9, 3.2 Hz), 137.0, 133.5, 127.8, 125.4 (q, J=282 Hz), 123.3, 121.8, 119.7, 117.8 (dd, J=19.8, 13.8 Hz), 117.2 (dd, J=19.2, 10.6 Hz), 112.7, 112.3 (ddd, J=26.1, 6.7, 3.3 Hz), 105.1, 57.1, 51.3, 44.8 (q, J=32.7 Hz), 35.2, 26.9, 14.5.
