Reaction Steps
Prepared using General Procedure 17: To a stirred solution of (R)-methyl 2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetate (13 mg, 0.02 mmol) in THF (0.5 mL) was added sodium borohydride (2.3 mg, 0.06 mmol) at room temperature. The reaction was heated to 75° C. and methanol (0.03 mL, 0.7 mmol) was added dropwise. After 1 h, the reaction was cooled and concentrated. Purification of the crude material by preparative HPLC gave 6 mg (60%) of (R)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyethanesulfonamide 46. LCMS-ESI (m/z) calculated for C23H24N4O4S2: 484.1; found 485.1 [M+H]+, tR=3.26 min. 1H NMR (400 MHz, CDCl3) δ 8.23 (dd, J=8.9, 2.3 Hz, 1H), 8.16 (d, J=2.3 Hz, 1H), 7.83 (d, J=7.7 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H), 7.43 (t, J=7.6 Hz, 1H), 7.11 (d, J=9.0 Hz, 1H), 5.19-4.96 (m, 1H), 4.87-4.63 (m, 3H), 4.17 (dd, J=8.2, 4.4 Hz, 2H), 3.53 (ddd, J=17.2, 8.8, 3.5 Hz, 1H), 3.46-3.34 (m, 2H), 3.32-3.11 (m, 1H), 2.86-2.59 (m, 1H), 2.19-1.97 (m, 1H), 1.48 (d, J=6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 166.83, 165.72, 161.71, 144.11, 141.85, 133.47, 133.26, 129.53, 127.99, 126.92, 126.58, 122.64, 115.51, 113.87, 103.79, 72.54, 58.86, 57.43, 55.67, 34.69, 31.27, 21.73. Chiral HPLC: (R)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyethanesulfonamide was eluted in MeOH, 96.2% ee, tR=12.58 min (Chiral Method 2).
