Nitrogen → 5-(But-1-yn-1-yl)-4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Participants

Reaction Conditions

Reaction Steps

Nitrogen was bubbled into a solution of 5-bromo-4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (19.7 g, 65.9 mmol; Intermediate 18) and DMA (60 mL). After 5 min, CuI (1.25 g, 6.6 mmol), Pd(OAc)2 (1.48 g, 6.6 mmol), dppf (3.66 g, 6.6 mmol), Cs2CO3 (34.3 g, 105.4 mmol), and but-1-yn-1-yltrimethylsilane (11.6 g, 92.3 mmol; Intermediate 35) were added sequentially with continued N2 bubbling. The resulting mixture was heated at 80° C. for 18 h under N2. The reaction mixture was diluted with EtOAc (900 mL) and H2O (500 mL) and then filtered. The organic layer of the filtrate was separated, and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine (3×100 mL), dried over anhydrous Na2SO4, concentrated, and purified by silica gel chromatography (1:30 EtOAc/petroleum ether) to give the title compound (15.2 g) as a white solid. 1H NMR (DMSO-d6, 400 MHz): δ 8.26 (s, 1H), 7.57 (d, 1H), 7.42 (dd, 1H), 5.87 (dd, 1H), 3.90-3.86 (m, 1H), 3.78-3.71 (m, 1H), 2.48 (q, 2H), 2.40-2.30 (m, 1H), 2.05-1.95 (m, 2H), 1.77-1.71 (m, 1H), 1.59-1.57 (m, 2H), 1.19 (t, 3H); LCMS: 273 (M+H)+.

Provenance & Evidence