4-BROMO-2-METHOXY-BENZONITRILE

A mixture of 4-bromo-2-fluoro-benzonitrile (15.0 g, 75.0 MMOL), methanol (30.4 mL, 350 MMOL) and potassium carbonate (31.1 g, 225 MMOL) in DMF (150 mL) was stirred under argon at 55 °C overnight. At this point TLC (100percent methylene chloride) revealed no starting material, and the reaction mixture was poured into ether (300 mL) and water (150 mL). The layers were separated, and the organic layer was washed with water (150 mL) and brine (50 mL), dried over MG2S04, filtrated, and concentrated under reduced pressure, providing (15.2 g, 95.5percent) OF 4-BROMO-2-METHOXY-BENZONITRILE AS a white SOLID. H-NMR (CDCI3) 8 7.41 (d, J = 8.1 Hz, 1H), 7.16 (dd, J = 8.1, 1, 6 Hz, 1H), 7.13 (d, J = 1, 6 Hz, 1H), 3.93 (s, 3H); MS GC-MS (M+ = 211; RT= 6.15 min).4-Bromo-2-methoxybenzonitrile4-Bromo-2-fluorobenzonitrile (10 g, 0.05 mol) was mixed with K2CO3 (20 g, 0.15 mol) and MeOH (9.5 mL, 0.23 mol) in DMF (100 mL) and heated to 55 Preparation 16: 2-methoxy-4-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2- yl)benzonitrile; Step I L 4-bromo-2-methoxybenzonitrile; A mixture of 4-bromo-2-fluorobenzonitrile (5.00 g, 25 mmol), methanol (10.0 ml_, 240 mmol), and potassium carbonate (10.6 g, 75.0 mmol) in N, N-dimethylformamide (5OmL) was stirred under nitrogen at 55°C for 16 h. The reaction was diluted with diethyl ether and water. The layers were separated. The organic layer was washed with water and brine, dried over magnesium sulfate, filtered, and concentrated to the title compound as a white solid (5.03 g, 95percent). Step 1: Preparation of the starting material: 4-bromo-2-methoxy-benzonitrile. A mixture of 4-bromo-2-fluoro-benzonitrile (15.0 g, 75.0 mmol), methanol (30.4 mL, 350 mmol) and potassium carbonate (31. Ig, 225 mmol) in DMF (150 mL) was stirred under argon at 55 To a solution of 9.22g (40.1mmol) of the compound obtained in the Manufacturing in 200mL of anhydrous dichloromethane were added 11.17mL (80.2mmol) of triethyamine and 8.09mL of anhydrous trifluoromethanesulfonic acid at 0°C, and the mixture was stirred for 30 minutes at the same temperature and for 1 hour at room temperature. Then, water was added to the reaction mixture and the mixture was extracted with dichloromethane. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (eluent: chloroform) to give 7.84g (92percent) of the title compound.[00198] Step 2: A solution of 4-bromo-2-methoxybenzamide (508 mg, 2.21 mmol) in anhydrous DCM (10 mL) was cooled to 0 [00198] Step 2: A solution of 4-bromo-2-methoxybenzamide (508 mg, 2.21 mmol) in anhydrous DCM (10 mL) was cooled to 0 Example 146; Preparation of [(3-Amino-6-bromo-benzofuran-2-yl)-(214-dichloro-phenyl .-methanone; Step 1: Preparation of the starting material : 4-bromo-2-methoxy-benzonitrile; A mixture of 4-bromo-2-fluoro-benzonitrile (15. 0 g, 75.0 mmol), methanol (30.4 mL, 350 mmol) and potassium carbonate (31.1g, 225 mmol) in DMF (150 mL) was stirred under argon at 55 °C overnight. At this point TLC (100percent methylene chloride) revealed no starting material, and the reaction mixture was poured into ether (300 mL) and water (150 mL). The layers were separated, and the organic layer was washed with water (150 mL) and brine (50 mL), dried over Mg2SO4, filtrated, and concentrated under reduced pressure, providing (15.2 g, 95.5percent) of 4-bromo-2-methoxy-benzonitrile as a white solid. 'H-NMR (CDCl3) 8 7.41 (d, J = 8.1 Hz, 1H), 7.16 (dd, J = 8.1, 1, 6 Hz, 1H), 7.13 (d, J = 1, 6 Hz, 1H), 3.93 (s, 3H); MS GC-MS (M+ = 211 ; RT= 6. 15 min).In a 1L round-bottomed flask, 53.94 g (270 mmol) of 4-bromo-2-fluorobenzonitrile was dissolved in 500 mL of THF. Sodium methoxide (21.99 g, 407 mmol) was added and the mixture was heated to reflux until TLC (SiO2 : CH2Cl2) showed complete consumption of starting material. The mixture was poured into 1N HCl and the THF was evaporated in vacuo. The remaining mixture was extracted with diethyl ether. The extract was dried (MgSO4) and filtered over a plug of silica gel. The plug was eluted with CH2Cl2 and the filtrate was evaporated in vacuo to afford 45.56 g (80percent) of the product as a white solid. 1HNMR (500 MHz, CDCl3) δ 7.42 (d, 1H), 7.17 (dd, 1H), 7.14 (d, 1H), 3.95 (s, 3H).To a stirred solution of 1H-imidazole-4-carbaldehyde (1.00 g, 10.41 mmol) in dioxane (5 mL) was added

Molecular Weight:212.04
XLogP3:3.1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:210.96328
Monoisotopic Mass:210.96328
Topological Polar Surface Area:33
Heavy Atom Count:11
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes