Reaction Steps
The solution of N-cyano-N'-phenylthiourea (0.98 g, 5.5 mmol, compound of Example 3, part A) and 6-acetyl-3,4-dihydro-2,2-dimethyl-3-hydroxy-4-amino-2H-1-benzopyran (1.0 g, 4.25 mmol, prepared according to Evans et al., J. Med. Chem., 1983, 26, 1582 and J. Med. Chem., 1986, 29, 2194) in dimethylformamide (6 ml) under argon was treated with 1-(3-dimethylaminopropyl)-2-ethylcarbodiimide hydrochloride (1.1 g, 5.5 mmol). The reaction was stirred at room temperature for 2 hours and then partitioned between 10% citric acid and ethyl acetate. The aqueous phase was reextracted with ethyl acetate and the combined extracts were washed with water, sodium bicarbonate and brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated and the residue was crystallized from ethyl acetate to yield the title compound (0.43 g), m.p. 182°-184° C.: 1H NMR (DMSO-d6) δ 9.45 (s, 1H), 7.82 (m, 3H), 7.44 (s, 3H), 7.25 (s, 1H), 6.96 (d, J=9.0 Hz, 1H), 6.0 (s, 1H), 5.1 (m, 1H), 4.15 (m, 1H), 3.8 (s, 1H), 2.61 (s, 3H), 1.52 (s, 3H), 1.29 (s, 3H); 13C NMR (CDCl3) δ 196.2, 159.3, 156.6, 137.6, 129.7, 129.1, 128.4, 124.7, 123.5, 123.3, 117.2, 116.6, 80.0, 71.2, 52.3, 26.7, 26.3, 18.6; IR (KBr) 3412.3, 2978.3, 2935.8, 2179.7, 1670.5, 1602.9, 1577.9, 1493.0, 1359.9, 1271.2, 1126.5 cm-1.
