3-BROMO-2-METHYLBENZONITRILE

Synthesis of N-{[3'-(aminomethyl)-2-methylbiphenyl-3-yl]methyl}-5- nitro-4-(4, 5, 7, 8-tetrahydroimidazo[4, 5-d]azepin-6(lH)-yl)pyrimidin-2-amine; A solution of 3-bromo-2-methyl-benzamide (500 mg, 2.340 mmol) and pyridine (0.60 mL, 7.42 mmol) in dichloromethane (10 mL) was cooled to 0 3-Bromo-2-methylbenzonitrile. 3-Bromo-2-methylbenzonitrile 3-Bromo-2-methylbenzonitrile. EXAMPLE 178 (1) 3-bromo-2-methylbenzonitrile [32-1] (hereinafter referred to as a compound [32-1]) To a solution of 3-bromo-2-methylbenzoic acid (2.06 g) in thionyl chloride (10 mL) was added N, N-dimethylformamide (0.1 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, the obtained residue was dissolved in tetrahydrofuran (10 mL), 28percent ammonia solution (10 mL) was added to the mixture at 0°C, and the mixture was stirred at 0°C for 10 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. Thionyl chloride (10 mL) was added to a solution of the above obtained residue in benzene (20 mL), and the mixture was stirred at 75°C for 2 hours. Ice water was added to the reaction mixture, and the mixture was neutralized by adding sodium hydrogen carbonate and then extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the titled compound (1.76 g) as a white solid. General procedure: A mixture of 4, 6-dichloropyrimidin-2-amine (2.5 g, 15.24 mmol), (3- cyanophenyl)boronic acid (2.016 g, 13.72 mmol), tetrakis(triphenylphosphine)palladium(0) (1.057 g, 0.915 mmol) and sodium carbonate (3.23 g, 30.5 mmol) in 1, 4-dioxane (60 mL), and water (5 mL) was degassed with nitrogen, then the resulting mixture was heated at 60C for two days. After cooled to room temperature (RT), the mixture was concentrated, then diluted with water, and extracted with dichloromethane (DCM, 3 x 30 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography on a silica gel column with 8% ethyl acetate (EtOAc) in dichloromethane to afford the desired product. LCMS calculated for C11H8ClN4 (M+H)+: 231.0. Found: 231.0.

Molecular Weight:196.04
XLogP3:2.7
Hydrogen Bond Acceptor Count:1
Exact Mass:194.96836
Monoisotopic Mass:194.96836
Topological Polar Surface Area:23.8
Heavy Atom Count:10
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes