A scaleable synthetic route is described to obtain 2-(4-acetylpiperadin-1-yl)-6-[3,5-bis(trifluoromethyl)phenylmethyl]-4-(2-methylphenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one (1, KRP-103) as a neurokinin (NK)(1) antagonist. The key step in the synthesis is the intramolecular cyclization of N-[3,5-bis(trifluoromethyl)phenylmethyl]-N-(3-hydroxypropyl)-4-chloro-6-(2-methylpheny...

Novel 1-trifluoromethyl-4-quinolone derivatives (8a,b) were synthesized, and the antibacterial activity of each was evaluated. An oxidative desulfurization-fluorination reaction was employed to introduce a trifluoromethyl group at the N-1 position as a key step. Among the derivatives, 8a was found to exhibit antibacterial activity comparable to that of norfloxacin (1) against Staphylococcus aur...

The first enantioselective, organocatalytic alpha-trifluoromethylation and alpha-perfluoroalkylation of aldehydes have been accomplished using a readily available iridium photocatalyst and a chiral imidazolidinone catalyst. A range of alpha-trifluoromethyl and alpha-perfluoroalkyl aldehydes were obtained from commercially available perfluoroalkyl halides with high efficiency and enantioselectiv...

In an attempt to synthesize DNA containing 2'-deoxy-5-(trifluoromethyl)uridine (1) using previously published protocols, we found that the trifluoromethyl group converted into a cyano group, resulting in DNA containing 5-cyano-2'-deoxyuridine (3). We show that nucleoside 1 can be incorporated into DNA using phosphoramidite 2 in combination with acetyl-protected deoxycytidine and phenoxyacetyl-p...

Organic extracts of six urine samples from children treated with nitisinone, a medicine against tyrosinemia type I, were investigated by (1)H and (19)F NMR spectroscopy. The presence of unchanged 2-[2-nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione (NTBC), 6-hydroxy-2-[2-nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione (NTBC-OH) and 2-nitro-4-trifluoromethylbenzoic acid (NTFA) as w...

The stereoselective synthesis of trisubstituted 2-trifluoromethyl pyrrolidines by asymmetric Michael addition/hydrogenative cyclization is described. The direct organocatalytic addition of 1,1,1-trifluoromethylketones to nitroolefins proceeds under mild reaction conditions and low catalyst loadings to provide Michael adducts in high yield with excellent diastereo- and enantioselectivity. Cataly...

Thiourea-based iminophosphorane (BIMP) organocatalysts featuring SPhos- or BIDIME phosphine units have been developed and successfully applied in the asymmetric addition of nitromethane to N-Boc-protected trifluoromethyl aryl ketimines. α-Trifluoromethyl β-nitroamines were obtained 40–82% isolated yields 80–95% enantioselectivities. A careful evaluation catalytic activity BIMPs indicates that c...

Diverse reactivity by coupling of substituted anilines with ethyl trifluoropyruvate was developed under microwave irradiation without catalysts to generate 3-trifluoromethyl-3-hydroxy oxindoles, aromatic hydroxy trifluoromethyl esters, and 1,2-dicarbonyl compounds in a fast and efficient manner. The plausible mechanism for obtaining different products was proposed. Furthermore, the anti-HIV act...

The first syntheses of fluorine-18 labeled inhibitors of GABA reuptake [(R,S)-1-[2-[4-[18F]fluorophenyl]phenyl]methoxyethyl]piperidine- 3-carboxylic acid, (R,S)-1-[2-[(4-[18F]trifluoromethyl)phenyl][(4- trifluoromethyl)phenyl]-methoxyethyl]piperidine-3-carboxylic acid] are described. These N-substituted nipecotic acid derivatives were prepared in no-carrier-added form by the condensation of the...

A simple and practical method for the determination of rate constants for trifluoromethyl radical addition to various alkenes by applying competition kinetics is introduced. In the kinetic experiments the trifluoromethyl radicals are generated in situ from a commercially available hypervalent-iodine-CF3 reagent (Togni-reagent) by SET-reduction with TEMPONa in the presence of TEMPO and a π-accep...