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Methyl 2-amino-5-nitronicotinate is a useful chemical for the synthesis of polyfunctionalized benzo[d]thiazole and its aza analog thiazolo[5,4-b]pyridine.

Methyl 2-aminopyridine-3-carboxylate (10.0 g, 72.4 mmol) was added slowly dropwise from concentrated nitric acid (65%, 3.2 mmol, 76 mmol, 1.05 eq.) to a stirred suspension of concentrated sulfuric acid (96%, 90.5 mL, 1.69 mol, 23.3 eq.) at 0 °C. The reaction mixture was gradually brought to room temperature and stirred continuously for 2 hours. The resulting brown mixture was carefully poured into ice water and solid Na2CO3 was added by batchwise addition until complete neutralization (pH > 8). Subsequently, the aqueous layer was extracted three times with ethyl acetate (AcOEt). The combined organic layers were washed sequentially with saturated saline and deionized water and dried over anhydrous magnesium sulfate (MgSO4). Finally, the solvent was removed by vacuum evaporation to afford the target product 2-amino-3-carboxylic acid methyl ester-5-nitropyridine (11.7 g, 82% yield) as a colorless solid with a purity meeting the analytical requirements.

[1] Tetrahedron, 2014, vol. 70, # 35, p. 5541 - 5549
[2] Patent: WO2015/189595, 2015, A1. Location in patent: Page/Page column 48; 49
[3] Patent: EP1782811, 2007, A1. Location in patent: Page/Page column 42
[4] Patent: EP1669348, 2006, A1. Location in patent: Page/Page column 50