2-AMINO-5-BROMO-3-METHYLBENZOIC ACID

General procedure: Bromine (3.43 mL, 130 mmol) was added to a solution of 2-amino-5-trifluoromethylbenzoic acid ethyl ester (5.34 g, 23 mmol) in DCM (26.5 mL) at room temperature. Step A: To a solution of 2-amino-3-methylbenzoic acid (10.0 g, 66 mmol) in DMSO was added 48percent aqueous hydrogen bromide (18.0 ml). The reaction solution was stirred at room temperature overnight and then quenched with saturated sodium bicarbonate. The resultant mixture was stirred overnight. Precipitation was collected by filtration and dried in vacuo to give 2-amino-5-bromo-3-methylbenzoic acid (13.0 g, 85percent) as a pink solid: To a solution of 2-amino-3-methylbenzoic acid (5.00 g, 33.1 mmol) in acetic acid (110 mL) at 0 General procedure: In a 100ml of round flask , add 20ml of 3-methyl-2-amino-benzoic acid, 50ml of DMF, 30ml mmol of N- chlorosuccinimide(or N- bromosuccinimide ) and after stirred atreflux for 3h, the reaction solution was poured into ice water and dilutehydrochloric acid acidifying to pH = 6. Filtered andthe resulting solid was washed small amount of ethanol to give a gray solidchlorinated or brominated anthranilate III.yield 83percent. Y selected from :cholrine and bromine.To a 100 ml round bottom flask was added 3.0 g of 20 mmol 3-methyl-2-aminobenzoic acid X, 30 ml of DMF, 6.7 grams of 30 millimoles of NCS (or 30 millimoles of NBS), After stirring for 3 hours, The reaction solution was poured into ice water, Dilute hydrochloric acid to pH = 6, filter, The resulting solid was washed with a small amount of ethanol to give 2-amino-3-methyl-5-halo-benzoic acid III, Gray solid, 4.6 grams or more, Yield is greater than 83percent.Y selected from:chlorine, bromine, The 2-amino-3-methyl-5-halo-benzoic acid III is selected from the group consisting of -2-amino-3-methyl-5-chlorobenzoic acid, 2-amino-3-methyl-5-bromo-benzoic acidTo a solution of 19-51 (15 g, 0.1 mol) in AcOH (80 mL) was added Br2 (5.1 mL, 0.1 mol) dropwise at 0 °C. The reaction mixturewas stirred at room temperature for 4 h. The mixture was diluted with EtOAc and basified with aqueous NaOH solution (4 N) to pH 7. The mixture was extracted with EtOAc, dried, and concentrated to afford the crude product, which was purified by column chromatography on silica gel (eluted with DCMIMeOH = 100:0 to 50:1) to afford 19-S2 (12.0 g, 52.2percent yield) as a white solid. LC/MS (ESI) m/z: 230 (M+H).Method AZ: 2-Amino-5-bromo-3-methylbenzoic acid (lvi-a) 40percent HBr (6.00 mL, 44.7 mmol, 5 eq) was added to a solution of 2-amino-3-methylbenzoic acid (1.23 g, 8.14 mmol, 1.0 eq) in DMSO (15 mL).The resulting mixture was stirred at room temperature overnight. A white precipitate formed during the course of the reaction.The reaction mixture was quenched with saturated aqueous NaHCO 3 to give a white solid, This was filtered and dried under vacuum to obtain 950 mg (51percent yield) of lvi-a as a white solid. LCMS m / z = 229.9 (M + 1) (Method B) (retention time = 1.20 min).Example 132 Step 4: 2-amino-5-bromo-3-methylbenzoic acidA mixture of 5-bromo-7-methylindoline-2, 3-dione (8 g, 0.033 mol), sodium chloride (4.5 g, 0.09 mol) and sodium hydroxide (3.6 g, 0.09 mol) was dissolved in water (96 mL) with stirring to give a yellow solution. The reaction mixture was cooled to 0°C and to this mixture was added slowly a solution of 30percent hydrogen peroxide (7 mL) and .sodium hydroxide (6.27 g) in 83 mL of water. The reaction mixture was stirred for another 1.5 h at 0°C and then quenched with glacial acetic acid to give a tan precipitate. The solid was filtered, washed thoroughly with cold water and dried under vacuum to afford the title compound (5.8 g, 75percent).

Molecular Weight:230.06
XLogP3:2.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:228.97384
Monoisotopic Mass:228.97384
Topological Polar Surface Area:63.3
Heavy Atom Count:12
Complexity:186
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes