A Practical Synthesis of 4-Amino-2-(Trifluoromethyl)nicotinic Acid

Abstract

A practical synthesis of 4-amino-2-(trifluoromethyl)-nicotinic acid is described. 2-(Trifluoromethyl)pyridine was lithiated using lithium 2,2,6,6-tetramethylpiperidide (LTMP) in the presence of 1,3-dimethyl-2-imidazolidinone (DMI) and followed by CO 2 quench to give the C-3 carboxylation product. Subsequent directed C-4 lithiation of carboxylation product afforded 4-iodo-2-(trifluoromethyl)nicotinic acid, which was coupled with tert-butyl carbamate under Pd-catalyzed conditions and followed by Boc deprotection to yield the title product in four steps and 50% overall yield.

Substituted-nicotinyl thiourea derivatives bearing pyrimidine moiety: synthesis and biological evaluation

“…Among these, substituted nicotinic acid and its derivatives such as agricultural and pharmaceutical intermediates are well established [8][9][10][11]. Moreover, acylthiourea derivatives are well-known scaffolds for a wide range of biological activities such as antioxidant, bactericidal, herbicidal, insecticidal and regulating activities for plant growth [12][13][14][15][16][17][18].…”

Synthesis of Quinazolin-4(3H)-ones via Amidine N-Arylation

“…We envisaged that a much shorter and convergent synthesis of 1 was attainable if amidine arylation of 2 could be accomplished (Scheme ). Though N -arylations have been well established for many compounds containing the −NH moiety including amines, amides, oxazodiones, carbamates, ureas, hydrazines, amidoximes, and amidine, , N -arylations with N -substituted amidines were unprecedented.…”