2-AMINO-5-CHLORO-NICOTINIC ACID METHYL ESTER

Piperazine A37 may be used in place of piperazine or a substituted piperazine in the above examples. Lithium 2-amino-5-chloronicotinateA solution of 2, 5-dichloronicotinic acid (20.2 g, 0.105 mol) in methanol (500 mL) was cooled to 0Performed in duplicate on identical scales in two pressure vessels, methyl 2, 5-dichloronicotinate (4.5 g, 22 mmol) was dissolved in ammonia solution (250 mL, 0.5 M in 1 , 4-dioxane; 0.125 mol). The pressure vessels were sealed and heated at (85 +/- 5) Performed in duplicate on identical scales in two pressure vessels, methyl 2, 5-dichloronicotinate (4.5 g, 22 mmol) was dissolved in ammonia solution (250 mL, 0.5 M in 1 , 4-dioxane; 0.125 mol). The pressure vessels were sealed and heated at (85 +/- 5) °C for 9 days. The two reaction mixtures were allowed to cool to room temperature, then combined and concentrated under reduced pressure to yield a white solid. Dissolution of the solid in 1 :1 acetone-MeOH (-500 mL), followed by adsorption onto silica gel (25 g) and then purification by flash column chromatography (25:10:1 hexane-CHA solution of 2, 5-dichloronicotinic acid A54 (20.2 g, 0.105 mol) in methanol (500 mL) was cooled to 0100 mmol (15.2 g) of methyl 2-aminonicotinate were reacted with 120 mmol (16.02 g) of N-chlorosuccinimide at 60 ° C for 6 hours. Acetonitrile as a solvent. After completion of the reaction, methyl 2-amino-5-chloronicotinate was obtained, which was allowed to stand at 0 ° C for three hours. The solid was collected by filtration and dried to give a solid of methyl 2-amino-5-chloronicotinate and the acetonitrile was recovered. 17.3 g of product was obtained with a yield of 93percent.A solution of LiOH-H2O (1.38 g, 33 mmol) in water (33 mL) was added in one portion to a suspension of A solution of LiOH-H2O (1.38 g, 33 mmol) in water (33 mL) was added in one portion to a suspension of A solution of 2, 5-dichloronicotinic acid A54 (20.2 g, 0.105 mol) in methanol (500 mL) was cooled to 00C and neat thionyl chloride (38 mL, 63 g, 0.525 mol) was added over -30 min. The reaction mixture was stirred at 0°C for 1 hour. The cooling bath was removed, the reaction temperature was allowed to warm to rt, and the reaction was allowed to stir for an additional 2 days at room temperature and the solvent was removed under reduced pressure to give an off-white residue. The residue was dissolved in Et.2psi (-500 mL) and the resulting solution was washed successively with saturated aqueous NaHCO3 solution (-300 mL), water (-300 mL), and brine (-300 mL). The organic layer was separated, dried over anhydrous MgSO4, and filtered. Removal of the solvent under reduced pressure yielded methyl 2, 5-dichloronicotinate (21.0 g, 97percent) as a white solid.Performed in duplicate on identical scales in two pressure vessels, methyl 2, 5-dichloronicotinate (4.5 g, 22 mmol) was dissolved in ammonia solution (250 mL, 0.5 M in 1 , 4-dioxane; 0.125 mol). The pressure vessels were sealed and heated at (85 +/- 5) 0C for 9 days. The two reaction mixtures were allowed to cool to room temperature, then combined and concentrated under reduced pressure to yield a white solid. Dissolution of the solid in 1 :1 acetone-MeOH (-500 mL), followed by adsorption onto silica gel (25 g) and Piperazine A37 may be used in place of piperazine or a substituted piperazine in the above examples. Lithium 2-amino-5-chloronicotinateA solution of 2, 5-dichloronicotinic acid (20.2 g, 0.105 mol) in methanol (500 mL) was cooled to 00C and neat thionyl chloride (38 mL, 63 g, 0.525 mol) was added over -30 min. The reaction mixture was stirred at O0C for 1 hour. The cooling bath was removed, the reaction temperature was allowed to warm to room temperature, and the reaction was allowed to stir for an additional 2 days at room temperature. The solvent was removed under reduced pressure to give an off-white residue. The residue was dissolved in Et2O (-500 mL) and the resulting solution was washed successively with saturated aqueous NaHCO3 solution (-300 mL), water (-300 mL), and brine (-300 mL). The organic layer was separated, dried over anhydrous MgSO4, and filtered. Removal of the solvent under reduced pressure yielded methyl 2, 5-dichloronicotinate (21.0 g, 97percent) as a white solid. EPO Piperazine A37 may be used in place of piperazine or a substituted piperazine in the above examples. Lithium 2-amino-5-chloronicotinateA solution of 2, 5-dichloronicotinic acid (20.2 g, 0.105 mol) in methanol (500 mL) was cooled to 00C and neat thionyl chloride (38 mL, 63 g, 0.525 mol) was added over -30 min. The reaction mixture was stirred at O0C for 1 hour. The cooling bath was removed, the reaction temperature was allowed to warm to room temperature, and the reaction was allowed to stir for an additional 2 days at room temperature. The solvent was removed under reduced pressure to give an off-white residue. The residue was dissolved in Et2O (-500 mL) and the resulting solution was washed successively with saturated aqueous NaHCO3 solution (-300 mL), water (-300 mL), and brine (-300 mL). The organic layer was separated, dried over anhydrous MgSO4, and filtered. Removal of the solvent under reduced pressure yielded methyl 2, 5-dichloronicotinate (21.0 g, 97percent) as a white solid. EPO Performed in duplicate on identical scales in two pressure vessels, methyl 2, 5-dichloronicotinate (4.5 g, 22 mmol) was dissolved in ammonia solution (250 mL, 0.5 M in 1 , 4-dioxane; 0.125 mol). The pressure vessels were sealed and heated at (85 +/- 5) 0C for 9 days; The two reaction mixtures were allowed to cool to room temperature, then combined and concentrated under reduced pressure to yield a white solid. Dissolution of the solid in 1 :1 acetone-MeOH (-500 mL), followed by adsorption onto silica gel (25 g) and then purification by flash column chromatography (25:10:1 hexane-CH2CI2- Et2O), gave 6.08 g (75percent) of Performed in duplicate on identical scales in two pressure vessels, methyl 2, 5-dichloronicotinate (4.5 g, 22 mmol) was dissolved in ammonia solution (250 mL, 0.5 M in 1 , 4-dioxane; 0.125 mol). The pressure vessels were sealed and heated at (85 +/- 5) °C for 9 days. The two reaction mixtures were allowed to cool to room temperature, then combined and concentrated under reduced pressure to yield a white solid. Dissolution of the solid in 1 :1 acetone-MeOH (-500 mL), followed by adsorption onto silica gel (25 g) and then purification by flash column chromatography (25:10:1 hexane-CH2CI2- Et2O), gave 6.08 g (75percent) of methyl 2-amino~5-chloronicotinate.A solution of 2, 5-dichloronicotinic acid A54 (20.2 g, 0.105 mol) in methanol (500 mL) was cooled to 00C and neat thionyl chloride (38 mL, 63 g, 0.525 mol) was added over -30 min. The reaction mixture was stirred at 0°C for 1 hour. The cooling bath was removed, the reaction temperature was allowed to warm to rt, and the reaction was allowed to stir for an additional 2 days at room temperature and the solvent was removed under reduced pressure to give an off-white residue. The residue was dissolved in Et.2psi (-500 mL) and the resulting solution was washed successively with saturated aqueous NaHCO3 solution (-300 mL), water (-300 mL), and brine (-300 mL). The organic layer was separated, dried over anhydrous MgSO4, and filtered. Removal of the solvent under reduced pressure yielded methyl 2, 5-dichloronicotinate (21.0 g, 97percent) as a white solid.Performed in duplicate on identical scales in two pressure vessels, methyl 2, 5-dichloronicotinate (4.5 g, 22 mmol) was dissolved in ammonia solution (250 mL, 0.5 M in 1 , 4-dioxane; 0.125 mol). The pressure vessels were sealed and heated at (85 +/- 5) 0C for 9 days. The two reaction mixtures were allowed to cool to room temperature, then combined and concentrated under reduced pressure to yield a white solid. Dissolution of the solid in 1 :1 acetone-MeOH (-500 mL), followed by adsorption onto silica gel (25 g) and

Molecular Weight:186.59
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:186.0196052
Monoisotopic Mass:186.0196052
Topological Polar Surface Area:65.2
Heavy Atom Count:12
Complexity:177
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes