4-Bromo-5-chloro-2-nitrobenzenamine

Step 1: A mixture of 5-chloro-2-nitroaniline (6.0 g, 34.88 mmol) and NBS (6.06 g, 34.0 mmol) in HOAc (240mL) was stirred at 130 °C for 1 h. The reaction mixture was poured into water. The precipitate was collected by filtrationand washed with petroleum ether to give 4-bromo-5-chloro-2-nitroaniline as a light brown solid (8.25 g, 96.5percent). 1H NMR(300 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.62 (br s, 2H), 7.29 (s, 1H). LCMS (ESI) m/z 251 (M+H)+.[00669] A mixture of 5-chloro-2-nitrobenzenamine (17g, O. lmol), NBS (17g, O. lmol) and CH3COOH (210 ml) was stirred for 16 h at 25 °C. The reaction was quenched with water (100 mL) and extracted with ethyl acetate (1000 mL). The organic layer was washed with water (500 mL x 2), dried (Na2S04), filtered and concentrated in vacuo, the crude product was purified by chromatography (silica, ethyl acetate/petroleum ether =1/1) to afford 4-bromo-5-chloro-2-nitrobenzenamine (20g, 0.08mmol, 80percent) as a light yellow solid ESI-MS (EI+, m/z): 251 [M+H]+.6.OO g (34.768 mmol) of 5-chloro-2-nitroaniline and 6.06 g (34.073 mmol) of N-bromosuccinimide were dissolved in 240 ml acetic acid. The mixture was boiled under reflux for 45 min. After cooling, the reaction mixture was added to 1.5 1 water. The resultant precipitate was filtered off and dried under high vacuum. The residue was purified by preparative HPLC (eluent: acetonitrile/water, gradient 10:90 --> 90: 10). We obtained 6.75 g (75percent of theor.) of the target compound. LC-MS (method 4): R, = 1.19 min; MS (Elmin): m/z = 249 [M-H]30 g (0.117 mol) of 5-chloro-2-ntiroaniline (CAS 1635-61-6) was synthesized according to the synthetic method described in the reference WO WO 02-020363, Was dissolved in 200 ml of acetic acid (hereinafter referred to as AcOH, CAS 64-19-7)NBS 30 9g (0.174 mol) was added. The reaction solution was heated and stirred for 30 minutes, and it was confirmed that the reaction was completed. A large amount of water was poured into the reaction mixture to form precipitates, and 6 g (63.5percent) of intermediate 1-E was obtained in the same manner as in the extraction of intermediate 1-A .Example 45N

Molecular Weight:251.46
XLogP3:2.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:249.91447
Monoisotopic Mass:249.91447
Topological Polar Surface Area:71.8
Heavy Atom Count:12
Complexity:187
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes