Reaction Steps
To a solution of (R)-5-(3-(5-amino-5,6,7,8-tetrahydronaphthalen-1-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride 3 (20 mg, 0.05 mmol) in DMA (0.5 mL) was added TEA (136 μL, 0.97 mmol) and methylvinylsulfone (52 mg, 0.5 mmol). The reaction was heated to 80° C. for 24 h. The crude reaction mixture was purified by preparative HPLC to give (R)-2-isopropoxy-5-(3-(5-((2-(methylsulfonyl)ethyl)amino)-5,6,7,8-tetrahydronaphthalen-1-yl)-1,2,4-oxadiazol-5-yl)benzonitrile 48. LCMS-ESI (m/z) calculated for C25H28N4O4S: 480.6; found 481.2 [M+H]+, tR=2.58 min. 1H NMR (400 MHz, CDCl3) δ 8.37 (t, J=9.1 Hz, 1H), 8.31 (dd, J=8.9, 2.2 Hz, 1H), 8.08 (d, J=7.1 Hz, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.42 (t, J=7.7 Hz, 1H), 7.12 (d, J=9.1 Hz, 1H), 4.85-4.73 (m, 1H), 4.53 (t, J=5.0 Hz, 1H), 3.63 (dd, J=15.3, 4.0 Hz, 2H), 3.61-3.50 (m, 2H), 3.33-3.17 (m, 1H), 3.18-3.04 (m, 1H), 3.04 (d, J=8.6 Hz, 3H), 2.16 (ddd, J=29.6, 18.8, 12.2 Hz, 2H), 2.00 (dd, J=36.4, 18.4 Hz, 2H), 1.47 (d, J=6.1 Hz, 6H).
