Reaction Steps
Prepared using General Procedure 3: To a stirring solution of CDI ((9.5 mg, 0.06 mmol) in DCM (1 mL) were added dropwise a solution of (R)-5-(3-(5-amino-5,6,7,8-tetrahydronaphthalen-1-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile HCl salt 3 (20 mg, 0.05 mmol) and Et3N (20.3 μL, 0.15 mmol) in DCM (1 mL). After stirring for 15 h at room temperature, this solution was added dropwise to another solution containing (R)-3-dimethylaminopyrrolidine (18.6 mg, 0.15 mmol)) in DCM (1 mL) at room temperature. The reaction was stirred at room temperature for 6.5 h. The solvent was evaporated and the pure product was isolated by preparative HPLC to afford 17.5 mg (70%) of (R)-N-((R)-5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-3-(dimethylamino) pyrrolidine-1-carboxamide 20. LCMS-ESI (m/z) calculated for C29H34N6O3: 514.6; found 515.3 [M+H]+, tR=2.56 min. 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J=2.2 Hz, 1H), 8.31 (dt, J=8.7, 4.3 Hz, 1H), 7.91 (d, J=7.6 Hz, 1H), 7.52 (d, J=7.6 Hz, 1H), 7.34 (t, J=7.7 Hz, 1H), 7.12 (d, J=9.2 Hz, 1H), 5.13 (d, J=6.9 Hz, 1H), 4.86-4.73 (m, 1H), 4.64 (d, J=8.2 Hz, 1H), 3.91 (dd, J=10.4, 7.3 Hz, 1H), 3.80-3.56 (m, 3H), 3.41 (dd, J=17.5, 8.3 Hz, 1H), 3.15 (d, J=18.0 Hz, 1H), 3.10-2.93 (m, 1H), 2.85 (s, 6H), 2.46 (m, 2H), 2.05 (dd, J=9.2, 4.8 Hz, 1H), 1.88 (m, 3H), 1.45 (dd, J=13.9, 6.1 Hz, 6H).
