Sodium hydride (50 mg, 60%, 1.25 mmol) was added to a solution of cis-4-amino-1-cyclohexanecarboxylic acid (83 mg, 0.580 mmol) and anhydrous DMSO (2 mL) at rt under N2. After 10 min, 4-chloro-8-(cyclopentyloxy)-7-methoxy-2H-chromen-2-one (114 mg, 0.387 mmol, Example 7, Step 1) was added, and the mixture was stirred for 3 d, poured into 1M KH2PO4 and extracted with ethyl acetate. The extract was dried, filtered, concentrated, and purified by reverse-phase HPLC (30→100% MeCN/H2O) to give cis-4-(8-(cyclopentyloxy)-7-methoxy-2-oxo-2H-chromen-4-ylamino)cyclohexanecarboxylic acid: 1H NMR (400 MHz, DMSO-d6): δ 7.85 (d, 1H), 7.10 (d, 1H), 7.01 (d, 1H), 5.10 (s, 1H), 4.81 (m, 1H), 3.87 (s, 3H), 3.50 (m, 1H), 2.56 (m, 1H), 2.04 (m, 2H), 1.79-1.58 (m, 14H); MS (ESI): 402.0.
