2-Amino-5-bromoisonicotinic acid synthesis

Yield: 83%

Reaction Conditions:

Stage #1:methyl 2-amino-5-bromopyridine-4-carboxylate with water;lithium hydroxide in tetrahydrofuran;methanol at 70; for 2 h;Inert atmosphere;
Stage #2: with hydrogenchloride in tetrahydrofuran;methanol;water; pH=6 at 0;

Steps:

14.1
A mixture of compound 14-1 (10.0 g, 43.28 mmol) and LiOH (5.46 g, 129.8 mmol) in THF (400 mL), MeOH (200 mL) and water (100 mL) was stirred at 70 °C for 2 hrs under an atmosphere of N₂. Subsequently, the reaction mixture was cooled to 0 °C and adjusted its pH value to 6 by adding coned, aq. HC1. The resulting suspension was filtered and the solid was dried in vacuo to give compound 14-2 (7.8 g, 83% yield). LC-MS (ESI): m/z 211 [M+H]⁺.

References:

PRESIDIO PHARMACEUTICALS, INC.;ZHONG, Min;LI, Leping WO2012/58125, 2012, A1 Location in patent:Page/Page column 145