2-AMINO-3-BROMO-5-FLUOROBENZOIC ACID

N-Bromosuccinimide (631 mg, 3.55 mmol) was added portionwise to a stirred solution of 2-amino-5-fluorobenzoic acid (7, 500 mg, 3.22 mmol) dissolved in acetic acid (5 ml) and the reaction mixture was stirred overnight at room temperature. The resulting precipitate was collected by filtration, washed with petroleum ether (20 ml) and dried to a constant weight to afford 2-amino-3-bromo-5-fluorobenzoic acid (11, 501 mg, 66.4percent) as a clear beige solid, which was used without further purification: LCMS (t2-Amino-5-fluorobenzoic acid (20 g, 129 mmol) was dissolved in acetic acid (250 mL) at 0°C, and then N-bromosuccinimide(25 g, 140 mmol) was added in batchesto the above solution. The mixture was stirred at room temperaturefor 16 hours and then filtered. The filter cake was washed with petroleum ether (100 mL 3 3). The filter cake was driedin vacuo to deliver a white solid 21-g (18.8 g, yield: 62percent), this product was used without further purification. LC-MS(ESI): m/z = 234 [M+H]+.At 0° C., 2-amino-5-fluorobenzoic acid (20 g, 129 mmol) was dissolved in glacial acetic acid (250 mL), and N-bromosuccinimide (25 g, 140 mmol) was added thereto in portions. The preparation method is as follows: Its preparation method is:Using General procedure: The syntheses of compounds 3a-3x were mainly referred to literature method [35]. A mixture of 1a-1q, 1w, 1x (2mmol), EDC'HCl (575mg, 3mmol), HOBt (446mg, 3.3mmol), NH4Cl (348mg, 6.5mmol) and DIPEA (2.3mL, 13mmol) in DMSO (7mL) was stirred at room temperature for 15h. The mixture was extracted with EtOAc three times, and the combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 3a-3q, 3w, 3x. A mixture of 2r-2v (2mmol) and NH3·H2O (25-28wt%, 80mmol) in sealed tube was heated at 100C for 12h. The mixture was cooled to room temperature and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 3r-3v.

Molecular Weight:234.02
XLogP3:2.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:232.94877
Monoisotopic Mass:232.94877
Topological Polar Surface Area:63.3
Heavy Atom Count:12
Complexity:190
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes