2-Amino-5-bromo-3-pyridinecarboxamide

A mixture of 2-amino-5-bromonicotinic acid (2.0 g, 9.20 mmol), HOBT (1.40 g, 11.2 mmol), EDCI (3.52 g, 18.4 mmol), Et3N (4.68 g, 46.0 mmol) and NH4C1 (2.48 g, 46.0 mmol) in DMF (100 mL) was stirred overnight at room temperature. The reaction mixture was concentratedin vacuo, suspended in water and extracted with CH2C12. The organic layer was washed with brine, dried over Na2504 and concentrated to give the product of 2-amino-5-bromonicotinamide (1.80 g, yield: 80percent), which was used for the next step without further purification. ‘H NMR (DMSO-d6, 400 MHz) 8.14 (dd, J= 4.4 Hz, 2.4 Hz, 2H), 8.04 (s, 1H), 7.46 (s, 1H), 7.37 (s, 2H). MS (M+H):216/218.To an ice-cold suspension of 2-amino-5-bromo-nicotinic acid hydrobromide (5.11 g, 17.1 mmol) and ammonium chloride (9.15 g, 171 mmol) in dimethoxyethane (170 mL) was added Et3N (4.8 mL, 34.2 mmol). After 10 min, diethylphosphoryl cyanide was added dropwise and the cold bath removed. After 4 h, the solution was filtered and the filtrate concentrated. The resulting residue was partitioned between EtOAc and water. The organic layer was washed with satd NAHC03 (2 x) and satd NACL, dried (NA2SO4) and concentrated under reduced pressure. The yellow solid was dissolved in EtOAc and then hexanes were added until precipitation occurred. The solid was collected by filtration and then triturated with EtOAc to give the title compound (1.62 g, 44percent) as a yellow solid :APOS;H NMR (300 MHz, DMSO-d6) 8 8.13 (s, 2H), 8.04 (bs, 1H), 7.46 (bs, 1H), 7.37 (bs, 2H).A mixture of 2-amino-5-bromonicotinic acid (2.0 g, 9.20 mmol), HOBT (1.40 g, 11.2 mmol), EDCI (3.52 g, 18.4 mmol), Et3N (4.68 g, 46.0 mmol) and NH4C1 (2.48 g, 46.0 mmol) in DMF (100 mL) was stirred overnight at room temperature. The reaction mixture was concentratedin vacuo, suspended in water and extracted with CH2C12. The organic layer was washed with brine, dried over Na2504 and concentrated to give the product of 2-amino-5-bromonicotinamide (1.80 g, yield: 80%), which was used for the next step without further purification. 'H NMR (DMSO-d6, 400 MHz) 8.14 (dd, J= 4.4 Hz, 2.4 Hz, 2H), 8.04 (s, 1H), 7.46 (s, 1H), 7.37 (s, 2H). MS (M+H):216/218.A mixture of 2-amino-5-bromonicotinic acid (2.0 g, 9.20 mmol), HOBT (1.40 g, 11.2 mmol), EDCI (3.52 g, 18.4 mmol), Et3N (4.68 g, 46.0 mmol) and NH4C1 (2.48 g, 46.0 mmol) in DMF (100 mL) was stirred overnight at room temperature. The reaction mixture was concentrated in vacuo, suspended in water and extracted with CH2C12. The organic layer was washed with brine, dried over Na2S04 and concentrated to give the product of 2-amino-5- bromonicotinamide (1.80 g, yield: 80%), which was used for the next step without further purification. NMR (DMSO-i, 400 MHz) delta 8.14 (dd, J= 4.4 Hz, 2.4 Hz, 2H), 8.04 (s, 1H), 7.46 (s, 1H), 7.37 (s, 2H). MS (M+H)+: 216 / 218.A mixture of A mixture of To a mixture of To a mixture of Example 135 5-bromo-1-(3-chlorobenzyl)-2-imino-1, 2-dihydropyridine-3-carboxamide hydrobromide To a solution of To an ice-cold suspension of 2-amino-5-bromo-nicotinic acid hydrobromide (5.11 g, 17.1 mmol) and ammonium chloride (9.15 g, 171 mmol) in dimethoxyethane (170 mL) was added Et3N (4.8 mL, 34.2 mmol). After 10 min, diethylphosphoryl cyanide was added dropwise and the cold bath removed. After 4 h, the solution was filtered and the filtrate concentrated. The resulting residue was partitioned between EtOAc and water. The organic layer was washed with satd NAHC03 (2 x) and satd NACL, dried (NA2SO4) and concentrated under reduced pressure. The yellow solid was dissolved in EtOAc and then hexanes were added until precipitation occurred. The solid was collected by filtration and then triturated with EtOAc to give the title compound (1.62 g, 44%) as a yellow solid :'H NMR (300 MHz, DMSO-d6) 8 8.13 (s, 2H), 8.04 (bs, 1H), 7.46 (bs, 1H), 7.37 (bs, 2H).Oxalyl chloride (100 mL, 1.16 mmol) was added dropwise to a suspension of 2- amino-5-bromo-nicotinamide (500 mg, 2.31 mmol) in toluene (5 mL) and the resulting mixture was heated to reflux for 4 h. The reaction mixture was cooled and the mustard- colored solid which had formed was collected by filtration. The solid was washed with a small amount of water, MEOH, and then dried under high vacuum (40 C) overnight to give the title compound (435 mg, 77%) :'H NMR (300 MHz, DMSO-D6) 8 11.86 (s, 1H), 11.60 (s, 1H), 8.72 (d, J = 2.5 Hz, 1H), 8. 35 (d, J = 2.5 Hz, 1 H) ; 13C NMR (126 MHz, DMSO-d6) 8 161.4, 154.8, 151.2, 150.17, 137.8, 112.6, 111.6.

Molecular Weight:216.04
XLogP3:0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:214.96942
Monoisotopic Mass:214.96942
Topological Polar Surface Area:82
Heavy Atom Count:11
Complexity:164
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes