Nitrogen → (S)-5-(5-(1-((tert-butyldimethylsilyl)oxy)-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-fluorobenzonitrile

Participants

Reaction Conditions

Reaction Steps

Prepared using General Procedure 1. A solution of 5-(5-bromothiazol-2-yl)-2-fluorobenzonitrile THZ INT-2 (0.12 g, 0.42 mmol), (5)-tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)oxy)silane IND INT-6 (0.16 g, 0.42 mmol), potassium carbonate (0.176 g, 1.2 mmol) and 3:1 mixture of DME/H2O (2 mL) was degassed with N2 for 10 min before the addition of Pd(PPh3)4 (0.034 g, 0.03 mmol). The mixture reaction was degassed with N2 for additional 2 min and then heated under microwave at 90° C. for 1.5 h. Upon cooling, the reaction mixture was diluted with EA (20 mL) and washed with brine (20 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by silica gel flash chromatography (30% EA/hexanes) to produce 0.116 g (60%) of (S)-5-(5-(1-((tert-butyldimethylsilyl)oxy)-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-fluorobenzonitrile as a white solid. LCMS-ESI (m/z) calculated for C25H27FN2OSSi: 450.6; found 451.1 [M+H]+, tR=4.86 min (Method 1). 1H NMR (400 MHz, CDCL3) δ 8.30-8.14 (m, 2H), 7.95 (s, 1H), 7.45 (dd, J=7.0, 0.9, 1H), 7.32 (ddd, J=23.9, 14.6, 11.0, 3H), 5.32 (t, J=7.0, 1H), 3.19 (ddd, J=15.9, 8.8, 2.7, 1H), 2.95 (dt, J=16.1, 8.1, 1H), 2.59-2.40 (m, 1H), 2.08-1.89 (m, 1H), 0.94 (s, 9H), 0.17 (dd, J=13.7, 7.8, 6H).

Provenance & Evidence