3-Bromo-4-(bromomethyl)benzonitrile

To a stirred solution of 3-bromo-4-methyl-benzonitrile (2 g, 10.2014 mmol, 100 mass percent) in carbon tetrachloride (20 ml_, 100 mass percent) under argon, was added NBS (2.2 g., 12.2417 mmol, 99 mass percent) and benzoyl peroxide (0.123 g., 0.5101 mmol, 100 mass percent). The mixture was heated to 85°C for 18h. The reaction mass was diluted with water (50 ml) and extracted with ethyl acetate. Organics were washed again with water and brine, dried and evaporated to afford 3-bromo-4-(bromomethyl) benzonitrile (1.2 g, 4.4 mmol, 90 mass percent, 95percent Yield) as an off white solid solid. H NMR (400 MHz, chloroform-c) δ ppm 3.89 - 4.01 (m, 2 H) 6.61 - 6.77 (m, 1 H) 6.92 - 7.07 (m, 2 H) LCMS: RT 1.12-1.49 Min 274 [M+H] The compound 57 (804 mg, 4.04 mmol) was dissolved in carbon tetrachloride (8 mL), and then added with NBS (730 mg, 4.10 mmol) and benzoyl peroxide (7 mg, 0.0289 mmol). The resulting mixture was heated under the protection of nitrogen until reflux occurred, and was stirred overnight. The mixture was cooled to room temperature, filtered to remove insoluble substances and distilled under reduced pressure to remove the solvent, then dissolved in ethyl acetate (30 mL) and respectively washed with water (10 mL) and saturated saline solution (10 mL). After the solvent was removed by means of reduced pressure distillation, the resulting product was purified by using a silica column (200 to 300 mesh silica gel, ethyl acetate/petroleum ether=1/35 for elution) to obtain 3-bromo-4-cyanobenzyl bromide (58) (583 mg), with a yield of 52.5percent.To a stirred solution of 3-bromo-4-methyl-benzonitrile (2 g, 10.2014 mmol, 100 mass percent) in carbon tetrachloride (20 ml_, 100 mass percent) under argon, was added NBS (2.2 g., 12.2417 mmol, 99 mass percent) and benzoyl peroxide (0.123 g., 0.5101 mmol, 100 mass percent). The mixture was heated to 85°C for 18h. The reaction mass was diluted with water (50 ml) and extracted with ethyl acetate. Organics were washed again with water and brine, dried and evaporated to afford 3-bromo-4-(bromomethyl) benzonitrile (1.2 g, 4.4 mmol, 90 mass percent, 95percent Yield) as an off white solid solid. H NMR (400 MHz, chloroform-c) δ ppm 3.89 - 4.01 (m, 2 H) 6.61 - 6.77 (m, 1 H) 6.92 - 7.07 (m, 2 H) LCMS: RT 1.12-1.49 Min 274 [M+H] The compound 57 (804 mg, 4.04 mmol) was dissolved in carbon tetrachloride (8 mL), and then added with NBS (730 mg, 4.10 mmol) and benzoyl peroxide (7 mg, 0.0289 mmol). The resulting mixture was heated under the protection of nitrogen until reflux occurred, and was stirred overnight. The mixture was cooled to room temperature, filtered to remove insoluble substances and distilled under reduced pressure to remove the solvent, then dissolved in ethyl acetate (30 mL) and respectively washed with water (10 mL) and saturated saline solution (10 mL). After the solvent was removed by means of reduced pressure distillation, the resulting product was purified by using a silica column (200 to 300 mesh silica gel, ethyl acetate/petroleum ether=1/35 for elution) to obtain 3-bromo-4-cyanobenzyl bromide (58) (583 mg), with a yield of 52.5percent.General procedure: To a cold (0 °C, ice bath) solution of 1-alkyl-1H-pyrazol-4-ol (3.5 g, 35.7 mmol) and potassium carbonate (5.2 g, 37.5 mmol, 1.05 eq.) in N, N-dimethylformamide (118.9 mL, 0.3 M) was slowly added benzyl chloride (4.3 mL, 37.5 mmol, 1.05 eq.). The reaction mixture was stirred at 0-25 °C for 2 h and 50 °C for 18 h. The reaction mixture was diluted with ethyl acetate (500 mL) and water (500 mL). The aqueous layer was extracted with ethyl acetate (250 mL). The combined organic layers were washed with water (250 mL), brine (100 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by column chromatography.3-Bromo-4-(bromomethyl)benzonitrile (1) (8 g, 29.1 mmol), was dissolved in THF (80 mL) and DMF (80 mL) and the solution was stirred at room temperature under a nitrogen atmosphere. Di-tert- butylimino carboxylate (9.48 g, 43.6 mmol) and potassium carbonate (6.0 g, 43.6 mmol) were added and the reaction was heated at 100 °C overnight. The mixture was diluted with EtOAc (250 mL) and water (250 mL). The organic phase was collected and the aqueous phase was extracted with EtOAc (250 mL). The combined organic extracts were washed with brine (120 mL), dried (MgS04), filtered, and evaporated to dryness. The crude product was purified by trituration with the minimal amount of methanol (~20 mL) and the solid was collected via filtration to give the desired product (10.3 g, 86percent) as a white solid. NMR (400 MHz, CDCI3): 7.84 (1 H, d), 7.59 (1 H, dd), 7.23 (1 H, d), 4.88 (2H, s), 1 .46 (18H, s)

Molecular Weight:274.94
XLogP3:2.9
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:274.87682
Monoisotopic Mass:272.87887
Topological Polar Surface Area:23.8
Heavy Atom Count:11
Complexity:172
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes