2-Amino-5-chloropyridine-3-carboxylic acid

A solution of 2, 6-dichloropyridine-3-carboxylic acid (3 g, 0.0157 mol) in aqueous ammonia (30 mL) was heated in a sealed tube at 130°C for 12 h. The reaction mixture was concentrated and the resulting crude solid was triturated with diethyl ether to afford the title compound (2.5 g, 93percent). δIntermediates:; a) 2-Amino-6-chloronicotinic acid (Inter. 2); To 2, 6-dichloronicotinic acid (Inter. I)(I equiv) was added liquid ammonia (sufficient to make a 0.6M solution of substrate in ammonia). The suspension was sealed in a pressure vessel which was then heated slowly to 130°C. It was noted that at this temperature a pressure of 18 bar was observed. This temperature and pressure was maintained for a further 16 hours whereupon the mixture was cooled to room temperature. The pressure vessel was opened and the reaction poured into ice cold water (1 reaction volume). The resulting solution was acidified to pH 1-2 using concentrated HCl which caused a precipitate to form. The acidic mixture was allowed to warm to room temperature and was stirred like this for a further 30 minutes. The suspension was then extracted with diethyl ether (3 x 400 ml). The combined organic extracts were then filtered and the filtrate concentrated in vacuo to give a white solid which was dried further over PTo the appropriate amino acid (1 equiv) was added liquid ammonia (sufficient to make a 0.6M solution of substrate in ammonia). The suspension was sealed in a pressure vessel which was then heated slowly to 130 2-Amino-6-chloronicotinic Acid (Inter. 2) Example 140A Preparation Example A-1. 2, 6-Dichloronicotinic acid (0.38 g, 2 mmol) and copper (I) iodide (720 mg, 3.8 mmol) were added to liquid ammonia (approx. 20 mL) in a sealed tube at -78°C, which was heated for 25 hours (oil bath temperature: 115°C). To liquid ammonia (approximately 20mL) was added 2, 6-dichloro-nicotinic acid (0.38g, 2mmol) and copper(I) iodide (720mg, 3.8mmol) at -78°C in a sealed tube, and the solution was heated for 25 hours (the temperature of the oil bath was 115°C). The temperature of the oil bath was raised to 125°C, which was further heated for 14 hours 30 minutes. The reaction mixture was allowed to room temperature, and ammonia was evaporated. Methanol was added, insoluble matter was removed by filtration, and the filtrate was concentrated to obtain the title compound (0.25g, 1.45mmol, 72percent) as a solid. 2.1: 2-Amino-6-chloronicotinic acid Manufacturing Example 26-1-1 2-Amino-6-chloro-nicotinic acid; A mixture of 2, 6-dichloro-nicotinic acid (31 g, 0.14 mol) and 28percent aqueous ammonia solution (200 mL) was stirred in a sealed tube for 10 hours at 135° C. This reaction solution was cooled to room temperature, and the excess ammonia gas was removed under a reduced pressure. Water was added to the residue to a total of 1000 mL, the mixture was cooled to 0° C., and citric acid was added to a pH being about 6. The precipitated solids were filtered out to obtain the title compound (12 g, 49percent).A mixture of 2, 6-dichloro-nicotinic acid (31 g, 0.14 mol) and 28percent aqueous ammonia solution (200 mL) was stirred in a sealed tube for 10 hours at 135° C. This reaction solution was cooled to room temperature, and the excess ammonia gas was removed under a reduced pressure. Water was added to the residue to a total of 1000 mL, the mixture was cooled to 0° C., and citric acid was added to a pH being about 6. The precipitated solids were filtered out to obtain the title compound (12 g, 49percent). Preparation Example A-4. Tris(2-(2-methoxyethoxy)ethyl)amine (3.0mL, 9.4mmol) was added to a mixture of 2, 6-dichloronicotinic acid (40g (90percentpurity), 0.19 mol), acetamide (80g, 1.4mol), potassium carbonate (78g, 0.56mol), copper(I) chloride (0.93g, 9.4mmol) and xylene (80mL), which was stirred overnight at 145°C. After cooling, copper(I) chloride (0.46g, 4.6mmol) was added to the reaction solution, which was stirred overnight at 145°C. After cooling the reaction solution to 105°C, water (100mL) was added, the solution was stirred for 1 hour at the same temperature, and cooled down to room temperature. 5N hydrochloric acid (150mL) was added, the solution was neutralized with a citric acid aqueous solution, then, ethyl acetate was added, and the solution was filtered through Celite pad. The organic layer was washed with brine, then, the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate), recrystallization by the ethyl acetate-hexane was carried out to obtain the title compound (1.4g, 8.3mmol, 4.5percent) as white crystal. [Production Example 4-1-1B] 2-Amino-6-chloro-nicotinic acid Example 140A 2-Amino-6-chloro-nicotinic Acid A mixture of 2, 6-dichloro-nicotonic acid (17.77 g, 92.6 mmol) in concenterated aqueous ammonia (173 mL) at 200 psi, was heated to 130° C. for 24 h. The mixture evaporated and the residue was taken into water (200 mL) and neuteralized with conc HCl then extracted into ether (200 ml). The ether was evaporated off to yield 12 g of product (75percent). MS (DCI/NH3) m/z 173 (M+1)+.A. 2-amino-6-chloronicotinamide, cpd 1a HATU (1.65 g, 4.35 mmol) was added to a solution of To a solution of

Molecular Weight:172.57
XLogP3:1.5
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:172.0039551
Monoisotopic Mass:172.0039551
Topological Polar Surface Area:76.2
Heavy Atom Count:11
Complexity:165
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes