Reaction Steps
To a stirred solution of (R)-5-(3-(5-amino-5,6,7,8-tetrahydronaphthalen-1-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride 3 (100 mg, 0.24 mmol) in DCM (5 mL) at 0° C. were added TEA (170 μL, 1.2 mmol) and 2-chloroethanesulfonyl chloride (76 μL, 0.73 mmol). The reaction mixture was warmed to room temperature and stirred for 30 min. The solvent was removed and the product was purified by chromatography (EA/hexane) to give 83.0 mg (75%) of (R)-N-(5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)ethenesulfonamide INT-16 as a white solid. LCMS-ESI (m/z) calculated for C24H24N4O4S: 464.5; found 465.1 [M+H]+, tR=3.83 min. 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J=2.2 Hz, 1H), 8.32 (dd, J=8.9, 2.2 Hz, 1H), 7.96 (dd, J=7.7, 1.2 Hz, 1H), 7.62 (t, J=11.0 Hz, 1H), 7.38 (t, J=7.7 Hz, 1H), 7.12 (d, J=9.0 Hz, 1H), 6.66 (dt, J=26.0, 13.0 Hz, 1H), 6.38 (d, J=16.5 Hz, 1H), 6.03 (dd, J=10.1, 5.2 Hz, 1H), 4.86-4.73 (m, 1H), 4.68-4.57 (m, 1H), 4.50 (d, J=8.3 Hz, 1H), 3.18 (dt, J=18.1, 5.8 Hz, 1H), 3.02 (dt, J=18.1, 6.8 Hz, 1H), 2.15-1.96 (m, 2H), 1.97-1.79 (m, 2H), 1.48 (d, J=6.1 Hz, 6H).
