6-AMino-4-chloro-nicotinic acid

Concentrated sulfuric acid (98percent, 0.5 mL) was added dropwise to a stirred suspension of compound iii (0.020 g, 0.130 mmol) in water (1 mL). The reaction mixture was heated to 100°C for 18 h, cooled to room temperature and added dropwise to a slurry of ice in saturated sodium bicarbonate solution (2 mL). The pH after addition was pH~2. The resulting precipitate was filtered, washed with water (2 mL) and air-dried to give compound iv. (0.019 g, 0.110 mmol, 84percent) as a colourless powder, [M+H]Concentrated sulphuric acid (98percent, 0.5 mL) was added dropwise to a stirred suspension of compound 31 (0.020 g, 0.130 mmol) in water (1 mL). The reaction mixture was heated to 100 °C for 18 h, cooled to room temperature and added dropwise to stirred ice / saturated sodium bicarbonate solution (2 mL), giving pH ca. 2. The resulting precipitate was filtered, washed with water (2 mL) and air dried to give the title compound (0.019 g, 0.110 mmol, 84percent) as a colourless powder, m.p. >250 °C (from EtOH–water); (Found: C, 41.2; H, 2.85; N, 15.9; CEthyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and 1- hydroxybenzotriazole monohydrate were added to a stirred solution of compound iv in DMF (3 mL) at room temperature. After 15 min, the m-toluidine was added and the reaction mixture stirred at the specified temperature for 24 h. The mixture was cooled to room temperature, poured onto water and extracted with EtOAc (3 x 30 mL). The combined organic phase was washed with water (20 mL), saturated aqueous sodium bicarbonate (20 mL) and brine (2 x 20 mL), dried (MgS04), and reduced in vacuo to give the v as a crude brown gum, which was used in the next step without further purification.1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide methyl iodide (0.175 g, 0.630 mmol) and 1-hydroxybenzotriazole monohydrate (0.097 g, 0.630 mmol) were added to a stirred solution of compound 32 (0.072 g, 0.420 mmol) in DMF (2 mL) at room temperature. After 15 min, m-toluidine (77 muL, 0.714 mmol) was added and the reaction mixture stirred at room temperature for 18 h. The reaction mixture was poured onto water (5 mL) and extracted with EtOAc (2 × 10 mL). The combined extracts were washed successively with saturated sodium bicarbonate solution (10 mL), water (3 × 10 mL), and brine (10 mL), dried (MgSO4) and concentrated to give the crude 3-carboxamido-4-anilino intermediate as a brown gum. This was taken up in 1, 4-dioxane (2 mL), treated with ethyl isocyanate (23 muL, 0.300 mmol) and heated to 80 C for 18 h. The reaction mixture was cooled to room temperature, diluted with EtOAc (5 mL) and reduced in vacuo directly onto SiO2. Column chromatography (SiO2), eluting with 2:1 Petrol-EtOAc to neat EtOAc, afforded the title compound (0.029 g, 0.072 mmol, 17%).Concentrated sulfuric acid (98%, 0.5 mL) was added dropwise to a stirred suspension of compound iii (0.020 g, 0.130 mmol) in water (1 mL). The reaction mixture was heated to 100C for 18 h, cooled to room temperature and added dropwise to a slurry of ice in saturated sodium bicarbonate solution (2 mL). The pH after addition was pH~2. The resulting precipitate was filtered, washed with water (2 mL) and air-dried to give compound iv. (0.019 g, 0.110 mmol, 84%) as a colourless powder, [M+H]+ mJz = 173.0.Concentrated sulphuric acid (98%, 0.5 mL) was added dropwise to a stirred suspension of compound 31 (0.020 g, 0.130 mmol) in water (1 mL). The reaction mixture was heated to 100 C for 18 h, cooled to room temperature and added dropwise to stirred ice / saturated sodium bicarbonate solution (2 mL), giving pH ca. 2. The resulting precipitate was filtered, washed with water (2 mL) and air dried to give the title compound (0.019 g, 0.110 mmol, 84%) as a colourless powder, m.p. >250 C (from EtOH-water); (Found: C, 41.2; H, 2.85; N, 15.9; C6H5ClN2O2 requires C, 41.7; H, 2.90; N, 16.2%); deltaH (300 MHz, DMSO-d6); 8.49 (1H, s, 2-H), 6.96 (2H, br s, 6-NH2), 6.50 (1H, s, 5-H); deltaC (75 MHz, DMSO-d6); 163.3 (3-CO2H), 162.7 (6-C), 153.9 (2-C), 143.6 (4-C), 112.9 (3-C), 108.5 (5-C) ; numax/cm-1 (solid); 3378, 3035, 1687, and 1356; m/z (ES) 173.0 (100%, MH+); (Found MH+, 173.0114. C6H5ClN2O2 requires MH 173.0112); LC-MS; RT= 0.38 min, m/z (ES+) found MH+, 173.0.

Molecular Weight:172.57
XLogP3:0.7
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