6-Bromo-4-fluoro-1H-indole

A dry 100-mL round bottom flask is charged with 4-bromo-2-fluoro-6- nitrotoluene (1.3 g; 5.56 mmol; 1 eq.), A/, A/-dimethylformamide diisopropyl acetal (2.6 mL; 12.22 mmol; 2.2 eq.), triethylamine (0.85 mL; 6.1 1 mmol; 1.1 eq.), anhydrous DMF (5 mL) and the mixture is stirred at 130 °C for 2 h. After removal of the solvent, the residue is dissolved in a mixture of toluene (30 mL) and acetic acid (40 mL), followed by the addition of iron (6.2 g; 1 1 1.10 mmol; 20 eq.) and silica (6 g). The dark red mixture is heated to 100 °C with vigorous stirring, for 30 min. The mixture is then cooled to room temperature, diluted with EtOAc, filtered and the solids are thoroughly washed with EtOAc. The combined filtrates are washed with sat. aq. NaA dry 100-mL round bottom flask is charged with 4-bromo-2-fluoro-6- nitrotoluene (1.3 g; 5.56 mmol; 1 eq.), A/, A/-dimethylformamide diisopropyl acetal (2.6 mL; 12.22 mmol; 2.2 eq.), triethylamine (0.85 mL; 6.1 1 mmol; 1.1 eq.), anhydrous DMF (5 mL) and the mixture is stirred at 130 °C for 2 h. After removal of the solvent, the residue is dissolved in a mixture of toluene (30 mL) and acetic acid (40 mL), followed by the addition of iron (6.2 g; 1 1 1.10 mmol; 20 eq.) and silica (6 g). The dark red mixture is heated to 100 °C with vigorous stirring, for 30 min. The mixture is then cooled to room temperature, diluted with EtOAc, filtered and the solids are thoroughly washed with EtOAc. The combined filtrates are washed with sat. aq. NaTo a solution of A dry 100-mL round bottom flask is charged with 4-bromo-2-fluoro-6- nitrotoluene (1.3 g; 5.56 mmol; 1 eq.), A/, A/-dimethylformamide diisopropyl acetal (2.6 mL; 12.22 mmol; 2.2 eq.), triethylamine (0.85 mL; 6.1 1 mmol; 1.1 eq.), anhydrous DMF (5 mL) and the mixture is stirred at 130 C for 2 h. After removal of the solvent, the residue is dissolved in a mixture of toluene (30 mL) and acetic acid (40 mL), followed by the addition of iron (6.2 g; 1 1 1.10 mmol; 20 eq.) and silica (6 g). The dark red mixture is heated to 100 C with vigorous stirring, for 30 min. The mixture is then cooled to room temperature, diluted with EtOAc, filtered and the solids are thoroughly washed with EtOAc. The combined filtrates are washed with sat. aq. Na2S20s, sat. aq. NaHCG-3 and brine, dried over Na2S04 and concentrated in vacuo. The residue is purified by FCC (20% DCM in hexanes) to afford 6-bromo-4-fluoro-1 /-/-indole (814 mg; 3.75 mmol; 68%; UPLC purity: 99%).To a solution of 6-bromo-4-fluoro-lH-indole (500 mg, 2.34 mmol), 1-methyl-4-(4, 4, 5, 5- tetramethyl-l, 3, 2-dioxaborolan-2-yl)-IH-pyrazole (0.63 g, 3.04 mmol) and K2C03 (0.97g.7.01 mmol) in dioxane/H20 (10.0 mL, 4: 1) was added j1, 1?- bis(diphenylphosphino)ferrocenejdichloropalladium(II) (171 mg, 0.24 mmol). The mixture was heated to 120 C for 12 h under a nitrogen atmosphere. After cooling the reaction to room temperature, water (10 mL) was added and the mixture was extracted with EtOAc (10 mL x 3). The combined organic layers were washed with sat. aq. NaHCO3 (10 mL x 3), driedover anhydrous Na2SO4, filtered and concentrated in vacuo. The emde residue was purified by silica gel chromatography (petroleum ether / EtOAc = 3 : 1) to give the title compound (0.33 g, 66%) as a light yellow solid.

Molecular Weight:214.03
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:212.95894
Monoisotopic Mass:212.95894
Topological Polar Surface Area:15.8
Heavy Atom Count:11
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes