Nitrogen → 5-(But-1-yn-1-yl)-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Temperatur

80 °C

Nitrogen was bubbled into a solution of 5-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (7.5 g, 25.33 mmol) and DMA (100 mL). After 5 min, CuI (241 mg, 1.27 mmol), Pd(OAc)2 (284 mg, 1.27 mmol), dppf (704 mg, 1.27 mmol), K2CO3 (4.89 g, 35.46 mmol), and but-1-yn-1-yltrimethylsilane (4.46 g, 35.46 mmol) were added sequentially with continued N2 bubbling. The resulting mixture was heated at 80° C. for 10 h under N2. The reaction mixture was diluted with EtOAc (250 mL) and H2O (200 mL) and 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 (3×50 mL), dried over anhydrous Na2SO4, concentrated, and purified by silica gel chromatography (1:30 EtOAc/petroleum ether) to give the pure product as a yellow solid (3.6 g) and an impure product (2 g; further purified to give additional 1.47 g). 1H NMR (300 MHz, DMSO-d6): δ 8.19 (d, 1H), 7.68 (d, 1H), 7.26 (dd, 1H), 5.79 (dd, 1H), 3.92-3.87 (m, 1H), 3.69-3.60 (m, 1H), 2.47-2.34 (m, 1H), 2.43 (q, 2H), 2.07-2.02 (m, 2H), 1.76-1.69 (m, 1H), 1.57-1.50 (m, 2H), 1.17 (t, 3H); LCMS: 273 (M+H)+.

1. filtrationfiltered
2. customThe organic layer of the filtrate was separated
3. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
4. washThe combined organic layers were washed with brine (3×50 mL)
5. dry with materialdried over anhydrous Na2SO4
6. concentrationconcentrated
7. custompurified by silica gel chromatography (1:30 EtOAc/petroleum ether)

ORD-Eintrag

ord-c51711a3f65146588a3e2d17fc3d6f26

Quelldatensatz

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08299112B2