2-aMino-6-(trifluoroMethyl)nicotinic acid synthesis

Yield:-

Reaction Conditions:

Stage #1:2-chloro-6-(trifluoromethyl)pyridine-3-carboxylic acid with 2,4-Dimethoxybenzylamine at 100;
Stage #2: with trifluoroacetic acid for 0.5 h;

Steps:

24
Intermediate 242-Amino-6-(trifluoromethyl)nicotinic acidA solution of 2-chloro-6-(trifluoromethyl)nicotinic acid (1.87 g, 8.29 mmol) in (2,4- dimethoxyphenyl)methanamine (2.491 ml, 16.58 mmol) was heated to 100 ⁰C overnight. The reaction mixture was concentrated under vacuum and partitioned between water and DCM. Evaporation of the organic layer provided a dark brown residue, which was dissolved in TFA (2.55 ml, 33.16 mmol), and the resulting mixture was stirred for 30 minutes. The precipitate formed was discarded via filtration and concentration of the filtrate under reduced pressure gave a residue. This residue was dissolved in HCl (IN, 200 mL) and the aqueous solution was washed with Et₂O and evaporated under reduced pressure to give a solid. This solid was washed with DCM/Hexanes, dried in a vacuum oven overnight and characterized as the title product (2 g). LCMS: 207.0 [M+H]⁺.

References:

ASTRAZENECA AB;ASTRAZENECA UK LIMITED;CHUAQUI, Claudio, Edmundo;HUANG, Shan;IOANNIDIS, Stephanos;SHI, Jie;SU, Mei;SU, Qibin WO2010/38060, 2010, A1 Location in patent:Page/Page column 77