Reaction Steps
To a round bottom flask was added (1R,2R)—N1-(1-(4-nitrophenyl)azepan-4-yl)cyclohexane-1,2-diamine (70 mg, 0.211 mmol), THF (3 mL), and Et3N (0.029 mL, 0.211 mmol). To the resulting solution was added isocyanatobenzene (25.08 mg, 0.211 mmol). The reaction was stirred at rt overnight. After this time, the reaction mixture was concentrated. The resulting crude product was purified by RP prep-HPLC to give a mixture of 2 diastereomers. The mixture of two diastereomers was separated by chiral HPLC (chiral separation method A) to give the desired product, 1-((1R,2R)-2-((S)-1-(4-nitrophenyl)azepan-4-ylamino)cyclohexyl)-3-phenylurea (7 mg, 0.019 mmol, 6.7% yield) as a yellow solid. Anal. Calcd. for C25H33N5O3 m/z 451.5, found: 452.3 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 8.10 (d, J=9.35 Hz, 2H), 7.30-7.27 (m, 2H), 7.22 (t, J=7.70 Hz, 2H), 6.99 (t, J=7.15 Hz, 1H), 6.60 (d, J=9.35 Hz, 2H), 4.57 (br. s., 1H), 3.66-3.53 (m, 2H), 3.53-3.45 (m, 1H), 3.44-3.35 (m, 1H), 3.21 (d, J=4.95 Hz, 1H), 2.85-2.73 (m, 1H), 2.24 (td, J=10.31, 3.57 Hz, 1H), 2.09 (d, J=9.35 Hz, 2H), 1.97 (d, J=12.10 Hz, 1H), 1.90 (d, J=11.55 Hz, 2H), 1.73 (d, J=9.90 Hz, 2H), 1.69-1.61 (m, 2H), 1.44-1.34 (m, 2H), 1.23-1.07 (m, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 157.11, 153.29, 139.21, 136.84, 129.12, 126.49, 123.13, 120.06, 110.01, 60.75, 56.99, 56.15, 49.50, 45.82, 34.95, 33.49, 33.29, 32.63, 25.06, 24.85, 23.76.
