3-Aminoisonicotinic acid

Light yellow Cryst

Step 1 NaOH (10percent aqueous, 640 ml) was cooled to 7° C. and bromine (15 ml, 286.82 mmol) added dropwise. Pyrrolo[3, 4-c]pyridine-1, 3-dione (41.711 g, 281.6 mmol) was then added to the reaction mixture before it was heated to 80° C. for 30 minutes. Bromine (3. 5 ml, 69.0 mmol) was added to a solution of 10 percent aqueous sodium hydroxide (120 ml) at 0 C to give a pale yellow solution. To this solution was added 3, 4-pyridinedicarboximide (10 g, 67. 5 mmol) and the reaction was heated at 80 C for 45 min. The reaction was cooled in a water bath and acidified by the addition of acetic acid (12. 5 ml) causing precipitation. The solid was collected, rinsed with water(50 ml), thenMeOH(50 ml) and dried to give the title compound as a beige solid (6.28 g, 67 percent).1H NMR (360 MHz, DMSO)5 8. 06 (1H, s), 7.60(1H, d, J5. 1), 7.34(1H, d, J5. 1), 3.19 (2H, brs). M/z (ES+) 139 (M+H+).Following the procedures of Zhou et al (2001) Bioorg. Med. Chem. Lett.9(8):2061-2071, bromine (1.22 ml, 23.9 mmol) was slowly added to a cooled (5A solution of10percent aqueousNaOH (416 mL) was cooled to0 C and treated with bromine (28.2 g 176 mmol) portionwise via pipette while keeping the temperature below 5 C. To this mixture was added 3, 4-pyridinedicarboximide (25.78 g, 174mmol), and the cooling bath was removed. The reaction was heated to80 C for 45 min, then allowed to cool in an ice bath. When the temperature fell to 60 C, the dropwise addition of HOAc (50 mL) was started. Cooling was continued until the temperature reached 15 C. A yellow precipitate formed. The solid was filtered, rinsed with water, then dried under vacuum to give 14.9 g of product (108 mmol, 62percent). 1NMR IS-MS, m/e 139(m+1)Preparation 18 Step A: 3-Aminoisonicotinic acid: 2H-Pyrrolo[3, 4-c]pyridine-1, 3-dione (204.16 g, 1378.4 mmol) was dissolved in 10percent NaOH (3.3 L) and the solution was cooled to an internal temperature of 7° C. (ice/salt bath). Bromine (73.424 mL, 1433.5 mmol) was added dropwise while maintaining the internal temperature below 10° C. After completion of the addition, the reaction was heated to an internal temperature of 80-85° C. for 90 minutes. The reaction mixture was cooled to 20-30° C. in an ice bath then acetic acid (323.21 mL, 5651.2 mmol) was added dropwise. The reaction was stirred and cooled to 5° C. The solids were collected by vacuum filtration, washed with cold water then air-dried to provide the product (108.86 g, 57percent).Preparation 18 Preparation 18 Description 1 (3. 55 g, 25. 7 mmol), H2SO4 (2. 5 ml) and methanol(50 ml) were heated at 80 C for 3 days. The methanol was evaporated, the residue diluted with water(75 ml) and heated to 80 C. Solid sodium carbonate was added until effervescence ceased. The mixture was cooled and extracted with dichloromethane (2 x 100 ml). The combined organic layers were dried overMgS04 and concentrated to give the title compound as a beige solid (2.36 g, 60 percent). 'H NMR (500 MHz, DMSO) 5 8.24 (1H, s), 7.74 (1H, d, J5. 3), 7.46 (1H, d, J5.2), 6.67 (2H, brs), 3.83 (3H, s). M/z (ES+) 153 (M+H+).A mixture of 3-amino-isonicotinic acid (613 mg, 4.44 mmol), methanol (15 mL) and thionyl chloride (0.7 mL, 8.88 mmol) was stirred at reflux for 3 days. The volatiles were Step 1. To a suspension of commercially available 3-aminopyridine-4-carboxylic acid (4.84 g, 35.1 mmol) in pyridine (60 mL) wasadded dropwise ethyl chloroglyoxylate (9.58 g, 70.2 mmol) at 0 C, and the mixture was stirred at room temperature for 15 h. Thereaction mixture was concentrated under reduced pressure andthe residue was suspended with water. The resulting precipitatewas collected by filtration to give 3-(2-ethoxy-2-oxoacetamido)pyridine-4-carboxylic acid as a pale yellow powder (3.74 g, 45percent). 1H NMR (200 MHz, DMSO-d6) d 1.33 (3H, t, J = 7.0 Hz), 4.33(2H, q, J = 7.0 Hz), 7.88 (1H, d, J = 5.0 Hz), 8.53 (1H, d, J = 5.0 Hz), 9.71 (1H, s), 12.10 (1H, s).Step 2 To a suspension (60 mL) of 3-aminoisonicotinic acid (4.84 g, 35.1 mmol, 100percent) in pyridine was added dropwise ethyl chloroglyoxylate (9.58 g, 70.2 mmol) under ice-cooling, and the mixture was stirred at room temperature for 15 hrs. The reaction mixture was concentrated under reduced pressure and water was added to the concentrated residue to give a suspension. The insoluble material was collected by filtration to give, 3-{[(ethyloxy)(oxo)acetyl]amino}pyridine-4-carboxylic acid as a pale-yellow powder (3.74 g, 45percent). 1H-NMR (200 MHz, DMSO-d6) delta: 1.33 (3H, t, J=7.0 Hz), 4.33 (2H, q, J=7.0 Hz), 7.88 (1H, d, J=5.0 Hz), 8.53 (1H, d, J=5.0 Hz), 9.71 (1H, s), 12.10 (1H, s).Example 33 3-(Oxalyl-amino)-isonicotinic acid; To a stirred solution of 3-amino-isonicotinic acid (0.5 g, 3.62 mmol) and triethylamine (1 ml) in dry tetrahydrofuran (50 ml) at 0° C. was added dropwise ethyl oxalyl chloride (0.5 g, 3.69 mmol). The resulting reaction mixture was stirred at room temperature for 3 h, filtered and the volatiles were evaporated in vacuo. To the residue was added water (50 ml) and the resulting mixture was extracted with diethyl ether (2*50 ml). The organic phase was washed with saturated aqueous sodium chloride (50 ml), dried (MgSO4), filtered and the solvent evaporated in vacuo affording 0.4 g (46percent) of 3-(ethoxyoxalyl-amino)-isonicotinic acid as a solid.

3-Aminoisonicotinic acid is a biochemical reagent that can be used as a biological material or organic compound for life science related research.

Molecular Weight:138.12
XLogP3:0.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:138.042927438
Monoisotopic Mass:138.042927438
Topological Polar Surface Area:76.2
Heavy Atom Count:10
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes