Nitrogen → (S)-tert-butyl (4-(2-(3-cyano-4-fluorophenyl)thiazol-5-yl)-2,3-dihydro-1H-inden-1-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

Prepared using General Procedure 4. A solution of 5-(5-bromothiazol-2-yl)-2-fluorobenzonitrile THZ INT-2 (2.0 g, 7.0 mmol), (S)-tert-butyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate IND INT-17 (2.5 g, 7.0 mmol), potassium carbonate (2.9 g, 21 mmol) and a 3:1 mixture of DME/H2O (30 mL) was degassed with N2 for 10 min before the addition of Pd(PPh3)4 (0.57 g, 0.005 mmol). The mixture was degassed with N2 for an additional 2 min and the suspension was heated under nitrogen at 80° C. for 12 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 3.0 g (83%) of (S)-tert-butyl(4-(2-(3-cyano-4-fluorophenyl)thiazol-5-yl)-2,3-dihydro-1H-inden-1-yl)carbamate as a white solid. LCMS-ESI (m/z) calculated for C24H22FN3O2S: 435.5; found 436.1 [M+H]+, tR=4.14 min. 1H NMR (400 MHz, CDCl3) δ 8.20 (m, 2H), 7.93 (s, 1H), 7.44 (d, J=7.5 Hz, 1H), 7.32 (m, 3H), 5.26 (m, 1H), 4.76 (d, J=8.4 Hz, 1H), 3.09 (m, 2H), 2.65 (ddd, J=12.5, 8.3, 4.6 Hz, 1H), 1.84 (dq, J=12.9, 8.5 Hz, 1H), 1.48 (s, 9H).

Provenance & Evidence