N-(4-Bromo-2-nitrophenyl)acetamide

4-Bromo-2-nitroaniline 3a (30.3 g, 138 mmol) was dissolved in 240 mL of acetic acid, and acetic anhydride (22.44g, 220.2 mmol) was added, and the mixture was heated to 95 ° C for 7.5 hours. The reaction solution was cooled to room temperature and poured into 600 mL of ice water. After ice-melting, it was extracted with dichloromethane (90 mL×3), and the solid was dissolved in dichloromethane (600 mL), the organic phase was combined, dried over anhydrous sodium sulfate Concentration gave N-(4-bromo-2-nitrophenyl)acetamide 3b (35.4g, orange solid), yield: 99.1percent.A mixture of 4-bromo-2-nitroaniline 1a (100g, 460.79mmol) was dissolved in 10mL of dichloromethane, was added 1000mL of acetic acid, acetic anhydride (61.15g, 599.02mmol), was heated to 95 deg.] C for 5 hours.The unreacted starting material completely, additional acetic anhydride (4.70g, 46.08mmol), the reaction was continued 95 1 hour.The reaction was cooled to room temperature was added 2000mL of water, filtered, to the filtrate was added 500mL of water, filtered again, the filtrate was added 500mL of water was filtered again, all solids were combined, washed with 1000mL water and 1000mL saturated sodium bicarbonate solution, two solid was dissolved in 500mL chloride, and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give N- (4- bromo-2-nitrophenyl) acetamide 8a (162g, orange solid), yield: 67.9percentGeneral procedure: A flame-dried reaction vessel with a magnetic stirring bar was charged with substrate (0.2mmol), Bi(NOEXAMPLE 20 4-Bromo-2-nitroaniline 3a (30.3 g, 138 mmol) was dissolved in 240 mL of acetic acid, and acetic anhydride (22.44g, 220.2 mmol) was added, and the mixture was heated to 95 C for 7.5 hours. The reaction solution was cooled to room temperature and poured into 600 mL of ice water. After ice-melting, it was extracted with dichloromethane (90 mL×3), and the solid was dissolved in dichloromethane (600 mL), the organic phase was combined, dried over anhydrous sodium sulfate Concentration gave N-(4-bromo-2-nitrophenyl)acetamide 3b (35.4g, orange solid), yield: 99.1%.4-Bromo-2-nitroaniline 1a (6.00 g, 27.65 mmol) was dissolved in 45 mL of acetic acid, the solution was added with acetic anhydride (2.85 mL, 30.41 mmol), heated to 100 °C and reacted for 5 hours. The reaction solution was added with 100 mL of water, and a solid was precipitated, filtered, and the filter cake was dissolved in 50 mL of dichloromethane, the organic phase was washed with water (20 mL*2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain N-(4-bromo-2-nitrophenyl)acetamide 5a (6.60 g, yellow solid), yield: 92.1percent. MS m/z (ESI): 258.8 [M+1]A mixture of 4-bromo-2-nitroaniline 1a (100g, 460.79mmol) was dissolved in 10mL of dichloromethane, was added 1000mL of acetic acid, acetic anhydride (61.15g, 599.02mmol), was heated to 95 deg.] C for 5 hours.The unreacted starting material completely, additional acetic anhydride (4.70g, 46.08mmol), the reaction was continued 95 1 hour.The reaction was cooled to room temperature was added 2000mL of water, filtered, to the filtrate was added 500mL of water, filtered again, the filtrate was added 500mL of water was filtered again, all solids were combined, washed with 1000mL water and 1000mL saturated sodium bicarbonate solution, two solid was dissolved in 500mL chloride, and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give N- (4- bromo-2-nitrophenyl) acetamide 8a (162g, orange solid), yield: 67.9%N-(4-Bromo-2-nitrophenyl)acetamide 5a (1.00 g, 3.86 mmol), 1-cyclopropylpiperazine 8a (483.26 mg, 3.86 mmol), 4, 5-bis(diphenylphosphino)-9, 9-dimethylxanthene (446.71 mg, 0.772 mmol), tris(dibenzylideneacetone)dipalladium (353.48 mg, 0.386 mmol) and cesium carbonate (2.52 g, 7.72 mmol) were dissolved in 10 mL of toluene under the protection of argon, the solution was heated to 120 °C and reacted for 4 hours. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: B system) to obtain N-(4-(4-cyclopropylpiperazin-1-yl)-2-nitrophenyl) acetamide 8b (500 mg, red solid), yield: 42.7percent. MS m/z (ESI): 304.9 [M+1]

Molecular Weight:259.06
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:257.96400
Monoisotopic Mass:257.96400
Topological Polar Surface Area:74.9
Heavy Atom Count:14
Complexity:241
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes