Reaction Steps
Prepared using General Procedure 14. To a stirring solution of 5-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile 56 (50 mg, 0.1 mmol) in DCM (3 mL) was added thionyl chloride (25 mg, 0.21 mmol) at 0° C. The reaction mixture was stirred at room temperature for 3 h. The solvent was evaporated and the crude chloride re-dissolved in dimethyl acetamide (3 mL). Isopropyl ethylamine (40.8 mg, 0.316 mmol) and ethanolamine (19.3 mg, 0.31 mmol) were added and the reaction mixture heated at 70° C. overnight. The reaction mixture was quenched with NaHCO3 and extracted with EA. The combined organic extracts were washed with brine and then dried over MgSO4. The product was purified by chromatography (10% MeOH/DCM) to afford 25 mg (60%) of 5-(5-(1-(2-hydroxyethylamino)-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile 57. LCMS-ESI (m/z) calculated for C24H25N3O3: 403.5; found 404.1 [M+H]+, tR=2.41 min. 1H NMR (400 MHz, DMSO) δ 8.18 (t, J=2.3 Hz, 1H), 8.08 (dd, J=9.0, 2.3 Hz, 1H), 7.70 (d, J=7.7 Hz, 1H), 7.44 (d, J=17.4 Hz, 1H), 7.42-7.32 (m, 1H), 7.30-7.11 (m, 2H), 4.70 (dt, J=12.2, 6.1 Hz, 2H), 4.39 (s, 1H), 3.40 (t, J=5.0 Hz, 2H), 3.18-2.95 (m, 2H), 2.93-2.75 (m, 1H), 2.73-2.54 (m, 2H), 2.38-2.16 (m, 1H), 1.98-1.78 (m, 1H), 1.15 (d, J=6.0 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 161.35, 159.17, 151.04, 146.60, 139.78, 132.16, 127.43, 125.59, 125.07, 123.99, 120.49, 116.10, 113.90, 103.77, 72.60, 62.95, 61.51, 48.70, 33.27, 31.29, 29.91, 22.02.
