2-Amino-5-bromonicotinic acid

Light yellow powder

Step 1: Equipped with a blender, Reflux condenser 500mL three-necked flask, 20.7 g (0.15 mol) of 2-aminonicotinic acid, 80 mL acetic acid, Stirred at room temperature, A constant pressure dropping funnel was added dropwise with a mixed solution of 40 mL of acetic acid and 4.1 mL of bromine (0.08 mol)Drop end to continue mixing 4-5h.filter, Washed with acetic acid, dry, The solid was refluxed with methanol 100mL 10min 10min at room temperature, Filter and dry.31.2g of white solid was obtained, Yield 96percent.2-Amino-nicotinic acid (2 g, 14.48 mmol) was dispersed in glacial acetic acid. To this suspension was added a solution of bromine (1.2 mL) in glacial acetic acid (5 mL). The mixture was stirred at room temperature for 20 h. The mixture was filtered and washed with glacial acetic acid (10 mL) and water in several portions. The precipitate was collected and dried to give 2-amino-5-bromonicotinic acid (3.0 g, 95 percent yield) as yellow solid. 2-Amino-nicotinic acid (2 g, 14.48 mmol) was dispersed in glacial acetic acid. To this suspension was added a solution of bromine (1.2 mL) in glacial acetic acid (5 mL). The mixturewas stirred at room temperature for 20 h. The mixture was filtered and washed with glacial aceticacid (10 mE) and water in several portions. The precipitate was collected and dried to give 2-amino-5-bromonicotinic acid (3.0 g, 95 percent yield) as yellow solid. ‘H-NMR (DMSO-d6, 400 MHz) ö 8.31(d, J= 2.4 Hz, 1H), 8.18 (d, J= 2.8 Hz, 1H), 5.065.27 (m, 2H). MS (M+Hj: 218 / 220.2-Aminonicotinic acid (10.00 g, 72.40 mmol) was suspended in 40 ml of glacial acetic acid. To this suspension was added dropwise a solution of 4.82 ml (94.12 mmol) of bromine in 20 ml of glacial acetic acid. The mixture was stirred vigorouly at room temperature for 30 min. The formed precipitate was filtered off and washed with glacial acetic acid. The filter cake was collected and crystallized from the boiling methol to afford compound 8 as a white solid (14.5 g, 92percent yield). 1H NMR (300 MHz, DMSO-d6) δ 8.30 (d, J = 2.4 Hz, 1H), 8.16 (d, J = 2.4 Hz, 1H); MS (ESI, m/z): 216.8 [M+H]+.2-Amino-5-bromo-nicotinic acid: To a solution of pyridine-2-amino-3-carboxylic acid (2.05 g, 81.1 mmol) in AcOH (250 mL) was added bromine (11.0 mL, 199.2 mmol) at RT. The reaction mixture was stirred for 18 h at RT. On completion of the reaction, the solvent was evaporated completely under reduced pressure, filtered, washed with diethyl ether (3 x 75 mL) to afford the title compound as a yellow solid. Yield: 50.0 g (92.6percent) 'HNMR (DMSO-de, 400 MHz, TMS) δ: 11.7 (3H, br, s), 8.33 (1H, s), 8.20 (1H, s).2-aminonicotinic acid (10.0 g, 72 mmol) was dissolved in acetic acid (40 ml), Slowly add bromine (9.64 mL, 388 mmol) in acetic acid (20 mL), Stir at room temperature for 2 hours, filter by suction, and wash the filter cake with acetic acid.The cake was recrystallized from methanol, After suction filtration and drying, 14.1 g of a white solid is obtained.The yield is 90percent.This compound was prepared following a literature procedure.25 Toa suspension of 2-aminonicotinic acid 21 (3.75 g, 27 mmol) in glacialacetic acid (15 mL) was added a solution of bromine (1.8 mL, 35 mmol)in glacial acetic acid (3 mL) and the mixture was stirred at RT for 20 h.After completion monitored by TLC, the resulting precipitate was filteredand washed with glacial acetic acid 3 times. The remaining solidwas air dried and then recrystallised from boiling methanol to affordthe product 22 as white crystalline needles (5.2 g, 90percent). 1H NMR(400 MHz, d6-DMSO): δ 8.36 (1H, d, J=2.6 Hz), 8.25 (1H, d, J=2.6 Hz), 7.95–7.79 (2H, br.s); 13C NMR (100 MHz, d6-DMSO): δ166.6, 156.5, 149.9, 143.8, 109.3, 103.7. The spectroscopic data matchedthat reported in the literature.2-aminonicotinic acid (25.0 g, 181.00 mmol) was added to a well-dried 1000 mL three-neck round bottom flask, and acetic acid (150 mL) was added thereto. Bromine (11.85 mL, 230.02 mmol) was slowly added dropwise to acetic acid (50 mL). And the mixture was stirred at room temperature for 20 hours in a stream of nitrogen. The resulting product was poured into 500 mL of distilled water and stirred for 30 minutes. The product was filtered through a glass filter, washed with ether and acetone, and dried to obtain Compound 1 (27.4 g, yield 70percent).

Molecular Weight:217.02
XLogP3:1.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:215.95344
Monoisotopic Mass:215.95344
Topological Polar Surface Area:76.2
Heavy Atom Count:11
Complexity:165
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes