Reaction Steps
Prepared using General Procedure 16: To (R)-2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetic acid (20 mg, 0.04 mmol) in DCM (0.4 mL) was added HATU (45 mg, 0.12 mmol) and DIEA (10.3 mg, 0.08 mmol). After 30 min, dimethylamine (2M solution in THF, 200 μL, 0.4 mmol) was added and the reaction stirred for 18 h at room temperature. The reaction was quenched with water (100 μL) and the solvent evaporated. The crude material was purified by preparative HPLC to afford 14 mg (66%) of (R)-2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)-N,N-dimethylacetamide 43 as white solid. LCMS-ESI (m/z) calculated for C25H27N5O4S2: 525.2; found 526.2 [M+H]+, tR=3.42 min. 1H NMR (400 MHz, CDCl3) δ 8.20 (dd, J=8.9, 2.3 Hz, 1H), 8.14 (d, J=2.3 Hz, 1H), 7.82 (d, J=7.7 Hz, 1H), 7.73 (d, J=7.6 Hz, 1H), 7.40 (t, J=7.7 Hz, 1H), 7.09 (d, J=9.0 Hz, 1H), 5.50 (d, J=8.2 Hz, 1H), 5.07 (q, J=7.7 Hz, 1H), 4.76 (hept, J=6.1 Hz, 1H), 4.28 (d, J=14.6 Hz, 1H), 4.09 (d, J=14.6 Hz, 1H), 3.50 (ddd, J=17.0, 8.8, 3.4 Hz, 1H), 3.20 (dt, J=9.7, 7.1 Hz, 1H), 3.15 (s, 3H), 3.02 (s, 3H), 2.72 (dtd, J=11.4, 8.0, 3.5 Hz, 1H), 2.20 (dq, J=13.1, 8.4 Hz, 1H), 1.46 (d, J=6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 166.99, 165.73, 163.22, 161.71, 144.17, 141.92, 133.44, 133.34, 129.31, 127.92, 127.33, 126.37, 122.70, 115.57, 113.91, 103.71, 72.56, 59.23, 54.92, 38.30, 35.99, 31.36, 21.74. Chiral HPLC: (R)-2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)-N,N-dimethylacetamide was eluted in 40% IPA in hexanes, 100% ee, tR=22.87 min.
