Example 1
The starting material (4-((trans-4-aminocyclohexyl)oxy)benzoic acid) was prepared as previously described (Hwang et al, (2013) Bioorg. Med. Chem. Lett., 23:3732). To a solution of 4-((trans-4-aminocyclohexyl)oxy)benzoic acid (121 mg, 0.51 mmol) in dimethyl formamide (DMF, 10 mL) was added phenyl isocyanate (82 mg, 0.69 mmol). The reaction was allowed to stir overnight at which point ethyl acetate (EtOAc) and a solution of 1 M Na2CO3 was added and the aqueous layer was separated. A solution of 1 N HCl was added to the aqueous layer until pH=2 and the precipitates were filtered. The resulting product (103 mg, 0.29 mmol, 57%) was used without further purification. Melting point (MP)=241.2-252.9 (244.0)° C. 1H NMR (400 MHz, DMSO-d6) δ 12.60 (s, 1H), 8.29 (s, 1H), 7.87 (d, J=8.5 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H), 7.21 (t, J=7.7 Hz, 2H), 7.02 (d, J=8.6 Hz, 2H), 6.87 (t, J=7.4 Hz, 1H), 6.13 (d, J=7.5 Hz, 1H), 4.49-4.41 (b, 1H), 3.57-3.50 (b, 1H), 2.05 (d, J=11.4 Hz, 2H), 1.94 (d, J=10.5 Hz, 2H), 1.49 (q, J=10.5 Hz, 2H), 1.36 (q, J=10.5 Hz, 2H).
