Reaction Steps
Prepared using General Procedure 14: To a stirred solution of (S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile 4 (177 g, 0.47 mmol) and DIEA (182 mg, 1.4 mmol) in DCM (8 mL) was added freshly prepared ethyl-2-(chlorosulfonyl)acetate (131 mg, 0.7 mmol). After 45 min, the crude reaction was partitioned between DCM and NaHCO3. The organic layer was dried over MgSO4, concentrated, and purified by column chromatography (EA/hexanes) to provide 75 mg (30%) of (S)-ethyl 2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetate as light yellow solid. LCMS-ESI (m/z) calculated for C25H26N4O5S2: 526.1; found 527.1 [M+H]+, tR=3.71 min. 1H NMR (400 MHz, CDCl3) δ 8.16 (dd, J=8.9, 2.3 Hz, 1H), 8.09 (d, J=2.2 Hz, 1H), 7.76 (d, J=7.7 Hz, 1H), 7.57 (d, J=7.6 Hz, 1H), 7.35 (t, J=7.6 Hz, 1H), 7.03 (d, J=9.0 Hz, 1H), 5.46 (t, J=7.9 Hz, 1H), 4.70 (dt, J=12.2, 6.1 Hz, 1H), 4.26-4.17 (m, 2H), 4.00 (d, J=8.2 Hz, 2H), 3.49 (ddd, J=17.4, 9.5, 3.9 Hz, 1H), 3.26-3.05 (m, 1H), 2.56 (ddd, J=12.9, 9.0, 4.4 Hz, 1H), 2.23-2.08 (m, 1H), 1.41-1.37 (m, 6H), 1.28 (dd, J=11.7, 4.6 Hz, 3H).
