Efficient synthesis of new biheterocyclic 1-(5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-3-(6-trifluoro methylpyrimidin-4-yl)-propan-1-ones

Strategies for the Efficient Synthesis of Biheterocyclic 5-[2-(Trifluoromethylheteroaryl)-ethyl]-1,3,4-oxadiazoles from Levulinic Acid

“…16 For cyclocondensations between precursor 1 and amidine salts (hydrochloride or sulfate), we started the process based on a previous report on cyclocondensation [3 + 3] of 1,1,1-trifluoro-4-alkoxy-3-alken-2-ones and amidines under basic NaOH or alkoxy (methoxy, ethoxy) catalysis. 18 Initially, the cyclocondensation between 1 and 2-methyl-2-thiopseudourea sulfate was carried out in methanol via catalysis with 1 M NaOH aqueous solution at 25 °C for 1 h. This led to a good yield of 66% for pure methyl 3-(2-thiomethyl-6-trifluoromethylpyrimidin-4-yl) propanoate (2c). These conditions were extended to cyclocondensations between the precursor 1 and benzamidine hydrochloride, leading to methyl 3-(2-phenyl-6-trifluoromethyl pyrimidin-4-yl)propanoate (2b) at a good yield of 67%.…”

“…This substrate has three electrophilic centers allowing its use in [4 + 1], [3 + 2], and [3 + 3] cyclocondensation processes, as shown in Scheme 1. [14][15][16][17][18] Our ongoing interest in producing and understanding the biological activities of halogenated heterocyclic systems led us to study strategies for synthesizing a diversity of biheterocyclic systems, such as 5-[2-(trifluoromethylheteroaryl)-ethyl]-1,3,4-oxadiazoles (4)(5)(6)(7), with an ethylene spacer between heterocyclic nuclei, from methyl 3-(trifluoromethylheteroaryl)propanoates, where trifluoromethylheteroaryl is 5(3)-trifluoromethyl-1H-pyrazol-3(5)-yl, 2-phenyl-6-trifluoromethyl pyrimidin-4-yl, Vol. 28, No.…”

From Levulinic Acid to Biheterocycles: Synthesis of 1-[(5-Hydroxy-5-trifluoromethyl-3-substituted-4,5-dihydro-1H-pyrazol-1-yl)-3-(5-trifluoromethyl-1H-pyrazol-3-yl)propan-1-ones

“…This approach uses the versatility of the trifluoromethyl-substituted 1,3-dielectrophilic moiety for heterocycle diversification in the 3-position of the propanoic chain and the possibility of transforming the methyl ester into hydrazide; then, these new dinucleophiles are cyclocondensed with a wide range of 1,1,1-trifluoro-4-alkoxy-3-alken-2-ones (1) (Scheme 1). [14,15] In this work, we examined the synthesis of methyl (5-trifluoromethyl-1H-pyrazol-3-yl) propanoate from cyclocondensation of methyl 7,7,7-trifluoro-4-methoxy-6-oxo-4-heptenoate (1h) with hydrazine hydrochloride [16] and its conversion into the respective hydrazide derivative. We also performed cyclocondensation between propionylhydrazide derivative (3) and 1,1,1-trifluoro-4-methoxy-3-alken-2-ones (1a-k) to produce a new series of derivatives:…”