5-BROMO-3-CHLORO-1H-INDAZOLE

0.14 g (0.60 mmol) of 5-bromo-lH-indazole was dissolved in 4 mL of 1, 4-dioxane to which 0.084 g (0.60 mmol) of (2-fluorophenyl)boronic acid, 0.070 g (0.06 mmol) of tetrakis(triphenylphosphine)palladium(0) and 0.19 g (1.80 mmol) of sodium carbonate were dissolved in 1.0 mL of distilled water and added. After reacting with microwave reactor at 120 C for 15 minutes, the organic layer was separated, treated with magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was separated by column chromatography to give 0.11 g (74.2% yield) of 3-chloro-5-(2-fluorophenyl)-lH-indazole. 1H NMR (MeOD) delta: 7.80 (s, 1H), 7.69 (m, 3H), 7.58 (m, 1H), 7.19 (t, 2H)25 mL of tetrahydrofuran was added to 1.0 g (7.0 mmol) of zinc(II) chloride under nitrogen conditions to which 4.0 mL (7.0 mmol, 1.7 M tetrahydrofuran) of cyclopropyl magnesium bromide was added, followed by stirring at room temperature for 30 minutes. The reaction mixture was added to 0.4 g (1.72 mmol) of 5-bromo-3-chloro-lH-indazole under nitrogen conditions, and then reacted with microwave reactor at 100C for 10 minutes. The organic layer was separated and concentrated under reduced pressure. The residue was separated by column chromatography to give 0.24 g (80% yield) of 3-chloro-5-cyclopropyl- 1 H-indazole. 1H NMR (MeOD) delta : 7.36(d, 1H), 7.29(s, 1H), 7.18(d, 1H), 2.00(m, 1H), 0.95(d, 2H), 0.68(d, 2H)Under an Ar atmosphere, a mixture of 5-bromo-3-chloro-lH-indazo (1 g, 4.3 mmol), bis(pinacolato)diboron (2.2 g, 8.7 mmol), [l, l '-bis(diphenylphosphino)ferrocene]- dichloropalladium(II) (700 mg) and potassium acetate (1.26 g, 12.9 mmol) in 1, 4-dioxane (12 mL) was heated at 90 C overnight. The residue was partitioned between EtOAc and brine. The aqueous layer was separated and extracted with EtOAc. The combined organic layers were concentrated and the residue was purified by column chromatography to afford 3-chloro-5- (4, 4, 5, 5-tetramethyl-[l, 3, 2]dioxaborolan-2-yl)-lH-indazole (420 mg) which was directly used in the next step.Example 42 Synthesis of 5-Bromo-3-chloro-1H-indazole (CCXIV) To a room temperature solution of 3-chloro-1H-indazole (10.0 g, 65.5 mmol) in AcOH (250 ml) was added Br2 (3.54 ml, 68.8 mmol) dropwise. The reaction mixture was stirred at room temperature for 18 hours, then diluted with EtOAc (500 ml), washed with aqueous NaOH solution (10%), saturated aqueous NaHCO3 and brine. The organic layer was dried over MgSO4, filtered, concentrated, and the residue was recrystallized from toluene. The solid was washed with hexanes and dried in vacuo affording 5-Bromo-3-chloro-1H-indazole CCXIV as a white solid (54% yield).

Molecular Weight:231.48
XLogP3:3.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:229.92464
Monoisotopic Mass:229.92464
Topological Polar Surface Area:28.7
Heavy Atom Count:11
Complexity:155
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes