Reaction Steps
Prepared using General Procedure 19: To a CDI ((13.4 mg, 0.08 mmol) in DCM (0.5 mL) was added a suspension of (R)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 5 (20.0 mg, 0.04 mmol) and Et3N (14.7 mg, 0.14 mmol) in DCM (0.5 mL) and the mixture stirred for 2 h at room temperature. The resulting solution was added to the preparative solution of azetidin-3-ol hydrochloride (15.9 mg, 0.14 mmol)) at room temperature. The reaction was stirred at room temperature for 16 h. The solvent was evaporated and the crude material was purified by preparative HPLC to afford 15 mg of (62%) of (R)-N-((R)-4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)-3-(dimethylamino)pyrrolidine-1-carboxamide 56. LCMS-ESI (m/z) calculated for C28H32N6O2S: 516.2; found 517.2 [M+H]+, tR=2.43 min. 1H NMR (400 MHz, DMSO) δ 8.40 (d, J=2.4 Hz, 1H), 8.32 (dd, J=9.0, 2.4 Hz, 1H), 7.99-7.76 (m, 1H), 7.51 (d, J=9.2 Hz, 1H), 7.49-7.34 (m, 2H), 6.73 (d, J=8.4 Hz, 1H), 5.32 (d, J=8.2 Hz, 1H), 5.09-4.80 (m, 1H), 3.86 (dd, J=14.3, 7.0 Hz, 1H), 3.75 (dd, J=11.0, 7.5 Hz, 1H), 3.63-3.48 (m, 1H), 3.45-3.22 (m, 3H), 3.10 (dt, J=16.5, 8.3 Hz, 1H), 2.82 (t, J=5.1 Hz, 6H), 2.56-2.40 (m, 1H), 2.32 (dd, J=9.8, 2.5 Hz, 1H), 2.15-2.02 (m, 1H), 2.00-1.81 (m, 1H), 1.38 (d, J=6.0 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 167.10, 165.84, 161.80, 145.94, 142.30, 133.54, 133.36, 128.86, 127.82, 126.94, 126.41, 122.72, 115.78, 114.01, 103.72, 72.71, 64.71, 55.95, 46.76, 44.20, 42.04, 34.06, 31.45, 27.30, 21.90, 21.89.
