Some common heterocyclic compound, 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, molecular formula is C4H3F3N2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Computed Properties of C4H3F3N2
NMP (1.5 ml) was added to a mixture of 4-trifluoromethyl-1H-imidazole (65.8 mg, 0.484 mmol), methyl 3-iodo-6-methyl-2-pyridinecarboxylate D44 (67 mg), 4,7-bis(methyloxy)-1,10-phenanthroline (8.72 mg, 0.036 mmol), bis(copper(I) trifluoromethanesulfonate), benzene complex (6.09 mg, 0.012 mmol) and cesium carbonate (126 mg, 0.387 mmol) in a screw-topped vial with septum and the mixture was rapidly degassed via three vacuum/nitrogen cycles. The reaction mixture was then shaken and heated to 90 C. for 2 hours. The reaction mixture was heated to 110 C. for 2 hours. Another quantity of bis(copper(I) trifluoromethanesulfonate), benzene complex (6.09 mg, 0.012 mmol) was added and the mixture was heated with shaking to 110 C. for 2 hours. UPLC check shows all the methyl 3-iodo-6-methyl-2-pyridinecarboxylate has reacted but there are still only traces of the expected product methyl 6-methyl-3-[4-(trifluoromethyl)-1H-imidazol-1-yl]-2-pyridinecarboxylate-closer scrutiny showed that signals in the mass spectrum corresponding to the acid 6-methyl-3-[4-(trifluoromethyl)-1H-imidazol-1-yl]-2-pyridinecarboxylic acid co-elute with 4,7-bis(methyloxy)-1,10-phenanthroline in the UPLC. UPLC in basic conditions showed a better separation confirming the formation of the acid 6-methyl-3-[4-(trifluoromethyl)-1H-imidazol-1-yl]-2-pyridinecarboxylic acid as well as de-iodinated product. The reaction mixture was cooled, diluted with water (15 ml) and loaded onto an ENV+ cartridge (1 g). The cartridge was eluted with water and then with MeOH. UPLC check of the water washes indicated they contain NMP as well as the deiodinated product and the excess 4-trifluoromethyl-1H-imidazole. UPLC check of the MeOH washes indicated they contained the acid 6-methyl-3-[4-(trifluoromethyl)-1H-imidazol-1-yl]-2-pyridinecarboxylic acid plus some impurities. The MeOH washes were combined and evaporated under reduced pressure to give a dark brown residue which was purified on the Biotage (mobile phase A was water made up with 0.1% formic acid, mobile phase B was acetonitrile made up with 0.1% formic acid. 12M C18 column was eluted with phase A for 2 column volumes then in gradient 0-50% A/B). The fractions containing the acid of the desired product were not pure by UPLC-they were combined and evaporated under reduced pressure to give 35 mg of a solid residue which was further purified by FractionLynx (Acid LC1, note a considerable quantity of the solid was insoluble in DMSO/MeOH). The fraction containing the desired product was evaporated under reduced pressure to give the title compound D121 (9 mg) of a pale orange glass. UPLC (Basic GEN_QC): rt=0.38 minutes, peak observed: 272 (M+1). C11H8F3N3O2 requires 271.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 33468-69-8, its application will become more common.