3-Amino-5-chloro-2-pyridinecarboxylic acid

3-Amino-5-chloropyridine-2-carboxylic acid (Int 2, 2 g, 11.6 mmol) was dissolved in NMP (100 mL) together with 1-amino-2-methyl-propan-2-ol (CAS: 2854-16-2, 1.14 g, 12.8 mmol), triethylamine (3.56 mL, 25.6 mmol) and HATU (4.87 g, 12.8 mmol). The resulting mixture was stirred at room temperature overnight. Next, the mixture was diluted with water and extracted with EtOAc. The organic fractions were combined, concentrated and the resulting crude residue was purified by column chromatography (petroleum ether/EtOAc 95/5 to 50/50) to give 3-Amino-5-chloropicolinic acid (106) Conc. HCl (38%, 32 mL, d=1.20, 400 mmol) was added to 3-amino-5-chloropicolinamide (105) (2.3 g, 13 mmol). The mixture was stirred and heated to reflux. The resulting solution was refluxed (100 C.) for 17 h. The resulting mixture was cooled to room temperature, then placed in the cold room for 3 h. The mixture was filtered, leaving the title compound as its hydrochloride salt, 2.1 g (66%); mp 235-236 C. 1 H NMR (DMSO-d6): delta6.68 (bs, 2H), 7.33 (d, J=1.8 Hz, 1H), 7.80 (d, J=2.1, 1H).Step 2;. Preparation of 3-Amino-5-chloro-pyridine-2-carboxylic acid methyl ester; Heat at 90 C a mixture of 5-chloro-3-nitro-pyridine-2-carbonitrile (1.0 g, 5.90 mmol) and tin (II) chloride (6.79 g, 29.5 mmol) in ethanol (10 mL) for 3 h. Evaporate the solvent under reduced pressure, add a solution of 35% hydrochloric acid (5 mL) and reflux the mixture for 6 h. Concentrate the reaction in vacuo to dryness and dissolve the resulting residue in methanol (20 mL). Add thionyl chloride (0.95 mL, 7.08 mmol) at room temperature and heat the mixture at 90 C for 24 h. Remove the solvent under reduced pressure, add ethyl acetate, and wash with a saturated solution of sodium bicarbonate. Separate the organic layer, dry over sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue using silica gel chromatography, eluting with ethyl acetate to afford the title compound (0.77 g, 70%). H-NMR (CDCl3, 3 00 MHz): 8 3.97 (s, 3 H) ; 5.85 (bs, 2 H) ; 7.06 (d, J = 2.0 Hz, 1H), 7.97 (d, J = 2.0 Hz, 1H).Step 2;. Preparation of 3-Amino-5-chloro-pyridine-2-carboxylic acid methyl ester; Heat at 90 C a mixture of 5-chloro-3-nitro-pyridine-2-carbonitrile (1.0 g, 5.90 mmol) and tin (II) chloride (6.79 g, 29.5 mmol) in ethanol (10 mL) for 3 h. Evaporate the solvent under reduced pressure, add a solution of 35% hydrochloric acid (5 mL) and reflux the mixture for 6 h. Concentrate the reaction in vacuo to dryness and dissolve the resulting residue in methanol (20 mL). Add thionyl chloride (0.95 mL, 7.08 mmol) at room temperature and heat the mixture at 90 C for 24 h. Remove the solvent under reduced pressure, add ethyl acetate, and wash with a saturated solution of sodium bicarbonate. Separate the organic layer, dry over sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue using silica gel chromatography, eluting with ethyl acetate to afford the title compound (0.77 g, 70%). H-NMR (CDCl3, 3 00 MHz): 8 3.97 (s, 3 H) ; 5.85 (bs, 2 H) ; 7.06 (d, J = 2.0 Hz, 1H), 7.97 (d, J = 2.0 Hz, 1H).

Molecular Weight:172.57
XLogP3:1.2
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