2-Amino-6-chloronicotinamide

2-Amino-6-chloronicotinamide (Inter. 3) b) 2-Amino-6-chloronicotinamide (Inter. 3); To a 0.3 M solution of 2-amino-6-chloronicotinic acid (Inter. 2)(1 equiv) in anhydrous THF, under an inert atmosphere, was added thionyl chloride (3.3 equiv) in a dropwise fashion. The reaction mixture was stirred at room temperature for 2 hours. After this time the reaction was concentrated in vacuo to give a crude yellow solid residue. The crude solid was dissolved in THF (equal to initial reaction volume) and concentrated in vacuo again to give a yellow solid residue. The residue was dissolved once more in THF and concentrated as before to give a solid residue which was then dissolved in THF (to give a solution of 0.3M) and ammonia gas bubbled through the solution for 1 hour. The resultant precipitate was removed by filtration and the filtrate concentrated in vacuo to give a yellow precipitate which was triturated with water at 50°C then dried to give the title compound (92percent yield, 93percent purity), suitably clean to be used without any further purification, m/z (LC- MS, ESP): 172 [M+H]To a 0.3 M solution of amino acid (1 equiv) in anhydrous THF, under an inert atmosphere, was added thionyl chloride (3.3 equiv) in a dropwise fashion. The reaction mixture was stirred at room temperature for 2 hours. After this time the reaction was concentrated in vacuo to give a crude yellow solid residue. The crude solid was dissolved in THF (equal to initial reaction volume) and concentrated in vacuo again to give a yellow solid residue. The residue was dissolved once more in THF and concentrated as before to give a solid residue which was then dissolved in THF (to give a solution of 0.3M) and ammonia gas bubbled through the solution for 1 hour. The resultant precipitate was removed by filtration and the filtrate concentrated in vacuo to give a yellow precipitate which was triturated with water at 50 To a solution of 2-amino-6-chloronicotinic acid (1.0 g, 5.79 mmol), HOBT (932 mg, 6.95 mmol) and EDCI (2.22 g, 11.6 mmol) in 15 mL of DMF was added triethylamine (5.86 g, 57.9mmol) and NH4C1 (1.55 g, 28.9 mmol). Then the mixture was stirred at room temperature for 16 h. The solution was concentrated in vacuo to remove DMF and the residue was suspended in saturated NaHCO3. Finally the 2-amino-6-chloronicotinamide (800 mg, yield: 81percent) was obtained by filtration without further purification. ‘H-NMR (DMSO-d6, 400 MHz) 7.95 (d, J = 8.4 Hz, 1H), 7.62 (s, 2H), 7.39 (s, 2H), 6.59 (d, J = 8.4 Hz, 1H). MS (M+H): 172 / 174.Example 140B Example 140B 2-Amino-6-chloronicotinamide (Inter. 3) b) 2-Amino-6-chloronicotinamide (Inter. 3); To a 0.3 M solution of 2-amino-6-chloronicotinic acid (Inter. 2)(1 equiv) in anhydrous THF, under an inert atmosphere, was added thionyl chloride (3.3 equiv) in a dropwise fashion. The reaction mixture was stirred at room temperature for 2 hours. After this time the reaction was concentrated in vacuo to give a crude yellow solid residue. The crude solid was dissolved in THF (equal to initial reaction volume) and concentrated in vacuo again to give a yellow solid residue. The residue was dissolved once more in THF and concentrated as before to give a solid residue which was then dissolved in THF (to give a solution of 0.3M) and ammonia gas bubbled through the solution for 1 hour. The resultant precipitate was removed by filtration and the filtrate concentrated in vacuo to give a yellow precipitate which was triturated with water at 50°C then dried to give the title compound (92percent yield, 93percent purity), suitably clean to be used without any further purification, m/z (LC- MS, ESP): 172 [M+H]To a 0.3 M solution of amino acid (1 equiv) in anhydrous THF, under an inert atmosphere, was added thionyl chloride (3.3 equiv) in a dropwise fashion. The reaction mixture was stirred at room temperature for 2 hours. After this time the reaction was concentrated in vacuo to give a crude yellow solid residue. The crude solid was dissolved in THF (equal to initial reaction volume) and concentrated in vacuo again to give a yellow solid residue. The residue was dissolved once more in THF and concentrated as before to give a solid residue which was then dissolved in THF (to give a solution of 0.3M) and ammonia gas bubbled through the solution for 1 hour. The resultant precipitate was removed by filtration and the filtrate concentrated in vacuo to give a yellow precipitate which was triturated with water at 50 To a solution of 2-amino-6-chloronicotinic acid (1.0 g, 5.79 mmol), HOBT (932 mg, 6.95 mmol) and EDCI (2.22 g, 11.6 mmol) in 15 mL of DMF was added triethylamine (5.86 g, 57.9mmol) and NH4C1 (1.55 g, 28.9 mmol). Then the mixture was stirred at room temperature for 16 h. The solution was concentrated in vacuo to remove DMF and the residue was suspended in saturated NaHCO3. Finally the 2-amino-6-chloronicotinamide (800 mg, yield: 81percent) was obtained by filtration without further purification. ‘H-NMR (DMSO-d6, 400 MHz) 7.95 (d, J = 8.4 Hz, 1H), 7.62 (s, 2H), 7.39 (s, 2H), 6.59 (d, J = 8.4 Hz, 1H). MS (M+H): 172 / 174.Example 140B Example 140B A solution of Compound 14 (500mg, 2.90mmol), (CH3)3CHO (754mg, 8.80mmol) and CuCl2 (1.20g, 8.80mmol) were added into 5mL of ethanol. The obtained mixture was stirred at 75C for 12h. Then the mixture was filtrated and the filtrate was concentrated in vacuo and purified by column chromatography (CH2Cl2:CH3OH=20:1) to give compound 15 as white solid. Yield 29%; m.p. 121-123C. ESI-MS: 240.2 [M+H]+.

Molecular Weight:171.58
XLogP3:0.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:171.0199395
Monoisotopic Mass:171.0199395
Topological Polar Surface Area:82
Heavy Atom Count:11
Complexity:164
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes