Reaction Steps
Prepared using General Procedure 8: To a stirring solution of (R)-methyl 2-(N-(5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)sulfamoyl)acetate INT-14 (0.025 g, 0.05 mmol) in THF (25 mL) was added sodium borohydride (0.05 g, 0.12 mmol) at room temperature. The reaction was heated to 75° C. and methanol (0.02 mL, 0.05 mmol) was added. After 1 h, the reaction was cooled and concentrated and purified by preparative HPLC to give 16.0 mg (66%) of (R)-N-(5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-2-hydroxyethanesulfonamide 37. LCMS-ESI (m/z) calculated for C24H26N4O5S: 482.6; found 505.1 [M+Na]+, tR=3.46 min. 1H NMR (400 MHz, CDCl3) δ 8.39 (dd, J=5.4, 2.4 Hz, 1H), 8.35-8.25 (m, 1H), 7.95 (dt, J=7.7, 3.9 Hz, 1H), 7.67 (d, J=7.5 Hz, 1H), 7.43-7.32 (m, 1H), 7.12 (t, J=7.5 Hz, 1H), 4.80 (m, 3H), 4.12 (t, J=5.2 Hz, 2H), 3.46-3.28 (m, 2H), 3.17 (dt, J=18.0, 5.9 Hz, 1H), 3.02 (dt, J=18.1, 6.8 Hz, MX 2.68 (s, 1H), 2.12 (m, 1H), 2.07-1.82 (m, 3H), 1.47 (d, J=6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 172.82, 169.22, 162.81, 137.73, 136.90, 134.12, 133.89, 132.15, 130.28, 126.46, 126.33, 116.65, 115.22, 113.57, 103.93, 72.78, 57.32, 56.17, 52.54, 30.60, 28.06, 21.72, 19.04. Chiral HPLC: (R)-N-(5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-2-hydroxyethane sulfonamide 37 was eluted with 15% water/MeOH, (Chiral Method 2): 99.82% ee, tR=22.23 min.
