Ethyl 6-aminonicotinate

To a suspension of 6-amino nicotinic acid (1.0 gm, 7.23 mmol) in ethanol (20 mL) was added thionyl chloride (1.6 mL, 21.68 mmol) drop wise at 60 To a solution of 2-amino-5-pyridinecarboxylic acid (98; 5.0 g, 36.2 mmol) in ethanol (100 mL) was added SOClTo a stirred solution of 6-aminonicotinic acid (3 Kg, 21.61 mol) in ethanol (30 L)is added concentrated H2504 (3 L) and the reaction mixture is heated at 78 °C for 16 hours. The reaction mixture is cooled to room temperature and evaporated under reduced pressure. The residue is neutralized to pH —7.5 using saturated NaHCO3 solution andextracted with EtOAc (3x5 L). The combined organic extracts are washed with water(2x5 L), brine solution (5 L), dried over sodium sulphate, and evaporated to give the title compound as an off white solid (3.4 Kg, 93.87percent). LCMS m/z 167 (M+H)+To a stirred solution of 6-aminonicotinic acid (3 Kg, 21.61 mol) in ethanol (30 L) is added concentrated HHCl gas was passed through a solution of 6-amino-nicotinic acid (2.00 g, 14.5 mmol) in ethanol (40 mL) at 0° C. for 10 min, then warmed to reflux. [HC1] gas was passed through a solution of [6-AMINO-NICOTINIC] acid (2.00 g, 14.5 mmol) in ethanol (40 [ML)] at [0°C] for 10 min, then warmed to reflux. After 18 h, the mixture was allowed to cool, concentrated in vacuo to a colorless solid, which was partitioned with EtOAc and sat. aq. [NA2CO3.] The aqueous layer was separated and extracted with EtOAc. The combined organic layers were dried over [NA2SO4] and evaporated. Recrystallization in [ETOH] gave 2.20 g (92percent yield) of white solid that was typically used without further purification. [APOS;H] NMR (CDC1, ) : [No. ]8.75 (d, 1H, J = 2.1 [HZ), 8.] 07 (dd, 1H, J = 8.7, 2.1 Hz), 6.51 (d, 1H, J = 8.7 Hz), 4.96 (bs, 2H), 4.35 (q, 2H, J = 7.2 Hz), 1.40 (t, 3H, J = 7.2 Hz).To a solution of 2-amino-5-pyridinecarboxylic acid (150.0 g, 1.09 mol) in ethanol (2 L) was added thionyl chloride (259.0 g, 2.18 mol) at 0 °C. The mixture was heated at reflux for 12 h. The solvent was removed under reduced pressure. Saturated aq NaTo a solution of 2-amino-5-pyridinecarboxylic acid (150.0 g, 1.09 mol) in ethanol (2 L) was added thionyl chloride (259.0 g, 2.18 mol) at 0 °C. The mixture was heated at reflux for 12 h. The solvent was removed under reduced pressure. Saturated aq Na[0343] To a stirred solution of compound 1(150 g; 108.5 mmol; 1 eq) in ethanol (1.5 L) was added thionyl chloride (236 mL; 325 mmol; 3 eq) dropwise at 60 °C and the resulting mixture was heated at reflux for 17 h. The mixture was evaporated to dryness and the pH was adjusted to 7, using ice-cold saturated aqueous NaHCO3 solution and solid NaHCO3. The organic components were extracted from the aqueous phase with ethyl acetate (3 x 500 mL), and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate and the solvent was removed in vacuo to afford the title compound (152 g, 84percent) as an off-white solid. 1H NMR (CDC13) ö 8.71 (s, 1H), 7.99 (d, 1H, J = 12 Hz), 6.45 (d, 1H, J = 8 Hz), 4.95 (s, 2H), 4.31 (q, 2H, J= 8Hz); 1.35 (t, 3H, J= 8Hz). LCMS: m/z = 167.3 [M+Hf, RT = 2.32 minutes, (Program P1, Column Y).To a stirred solution of 6-aminonicotinic acid (300 mg, 2.51 mmol) in ethanol was slowly added thionyl chloride (0.55 mL, 4.34 mmol) at 0 °C. The reaction mixture was stirred overnight under reflux. Then the mixture was cooled to room temperature and the solvent was removed in vacuo. Then it was dissolved in ethylacetate and washed with saturated sodium bicarbonate solution. The organic layer was dried over MgS011.5 Grams (83 mmol) of 6-aminonicotinic acid (a) was dissolved in 85 ml of ethanol, 2.5 ml of concentrated sulfuric acid was added, and the mixture was refluxed under heat for 24 hours. The solvent was removed under vacuum, 150 ml of ice water was poured, and a saturated sodium hydrogen carbonate aqueous solution was added. The mixture was subjected to extraction with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated off under vacuum to give 10.0 g (yield 73 percent) of ethyl 6-aminonicotinate ester (b) in the form of a white solid.(a)

Molecular Weight:166.18
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:166.074227566
Monoisotopic Mass:166.074227566
Topological Polar Surface Area:65.2
Heavy Atom Count:12
Complexity:161
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes