Reaction Steps
Prepared using General Procedure 9: To a stirring solution of (R)-2-(N-(5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)sulfamoyl) acetic acid 34 (15 mg, 0.05 mmol) in DMF (0.5 mL) was added N-hydroxybenzotriazole (6.1 mg, 0.05 mmol) and EDC (8.7 mg, 0.05 mmol). After 5 min, dimethylamine (40 wt % solution in THF, 50 μL, 0.09 mmol) was added and the reaction mixture was stirred 18 h at room temperature. The crude reaction was diluted with sat NaHCO3 and extracted with EA. The combined organic layers were dried over Na2SO4 and purified by preparative HPLC to give 4.41 mg (28%) of (R)-2-(N-(5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)sulfamoyl)-N,N-dimethylacetamide 40. LCMS-ESI (m/z) calculated for C26H29N5O5S: 523.6; found 546.2 [M+Na]+, tR=3.58 min. 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J=2.1 Hz, 1H), 8.33 (dd, J=8.9, 2.2 Hz, 1H), 7.96 (dd, J=7.7, 1.2 Hz, 1H), 7.82 (d, J=7.5 Hz, 1H), 7.38 (t, J=7.8 Hz, 1H), 7.12 (d, J=9.0 Hz, 1H), 5.36 (t, J=17.3 Hz, 1H), 4.88-4.73 (m, 2H), 4.27 (d, J=14.6 Hz, 1H), 4.07 (d, J=14.6 Hz, 1H), 3.24-3.09 (m, 4H), 3.09-2.97 (m, 4H), 2.23-2.08 (m, 2H), 2.10-1.84 (m, 2H), 1.47 (d, J=6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 172.75, 169.37, 163.15, 162.77, 137.79, 136.92, 134.13, 133.90, 132.50, 130.18, 126.36, 126.17, 116.79, 115.25, 113.55, 103.96, 72.74, 55.46, 53.05, 38.22, 35.98, 29.84, 28.10, 21.73, 19.10.
