Methyl 2-amino-5-nitro-3-pyridinecarboxylate

Concentrated nitric acid (65percent, 3.2 mmol, 76 mmol, 1.05 equiv) was added dropwise to a stirred suspension of 21 (10.0 g, 72.4 mmol) in concentrated sulfuric acid (96percent, 90.5 mL, 1.69 mol, 23.3 equiv) maintained at 0 C.The solution was brought back to room temperature and stirred for 2 h. The brown mixture was poured onto iced water and carefully quenched by adding solid Na2CO3 portionwise until complete neutralization (pH>8). The aqueous layerwas extracted three times with AcOEt. The combined organic layers were washed with brine and water, and dried over MgSO4. Evaporation of the residue in vacuo furnished the title compound 22 in analytically pure form(11.7 g, 82percent) as a colourless solidA solution of 2-amino-3-nicotinic acid methyl ester (4 g, 26 mmol) in a mixture of concentrated HN0Preparation Example A-3 2-Amino-nicotinic acid methyl ester (1.00g, 6.57 mmol) described in Preparation Example A-2 was dissolved at 0°C in a mixed solution of nitric acid (0.7mL) and sulfuric acid (2.6mL), which was stirred at 0°C for 40 minute and at room temperature for 19 hours, then, further stirred at 70°C for 4 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction solution at 0°C, which was extracted with ethyl acetate and tetrahydrofuran, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo. Methanol was added to the residue, the precipitated solid was filtered to obtain the title compound (459mg, 2.33mmol, 35percent) as a white solid.

Molecular Weight:197.15
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:2
Exact Mass:197.04365571
Monoisotopic Mass:197.04365571
Topological Polar Surface Area:111
Heavy Atom Count:14
Complexity:240
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes