Abstract
Copper-catalyzed Csp2–Csp2 bond forming reactions through C–H activation are still one of the most useful strategies for the diversification of heterocyclic moieties using various coupling partners. A catalytic protocol for the C–H (hetero)arylation of thiazolo[5,4-f]quinazolin-9(8H)-ones and more generally fused-pyrimidinones using catalyst loading of CuI with diaryliodonium triflates as aryl source under microwave irradiation has been disclosed. The selectivity of the transfer of the aryl group was also disclosed in the case of unsymmetrical diaryliodonium salts. Specific phenylation of valuable fused-pyrimidinones including quinazolinone are provided. This strategy enables a rapid access to an array of various (hetero)arylated N-containing polyheteroaromatics as new potential bioactive compounds.
Highlights
Bi-heterocylic structures are found in many bioactive compounds and fused pyrimidinones represent a relevant substructure in medical chemistry, exhibiting a broad range of pharmacological activities
C–H arylation of azaheteroarenes [29,41,42,43,44,45,46], the reac2a as model substrates was first explored under metal-catalyzed (palladium or coppe tion of the N -benzylthiazolo[5,4-f ]quinazolin-9(8H)-one 1 with diphenyliodonium triflate and metal-free C–H arylation conditions (See Table S1, Supplementary Material)
2a as model substrates was first explored under metal-catalyzed palladium or metal-free catalysis, less than 10% of the phenylated product 3a was o and metal-free C–H arylation conditions
Summary
Fused-Pyrimidinone DerivativesBi-heterocylic structures are found in many bioactive compounds and fused pyrimidinones represent a relevant substructure in medical chemistry, exhibiting a broad range of pharmacological activities. Our group has previously reported the selective palladium-catalyzed and copper assisted C2–H arylation of quinazolin-4-ones, pyrido-pyrimidin-4-ones (see (a) in Scheme 1a) and thiazolo[5,4-f ]quinazolin-9(8H)-one under microwave irradiation (Scheme 1b) [9,10,11,12,13,14] This aforementioned heterocycle was used as a versatile scaffold for Structure Activity Relationship (SAR) studies in DYRK1A kinase inhibition involved in the field of neurodegenerative diseases [15,16,17] and cancer therapy [18,19,20]. The developed synergistic Pd/Cu catalysis suffers from some limitations, including the use of a large amount of transition-metal catalysts and poor reactivity of certain classes of substrates This strategy was proved to be inefficient in some fused-pyrimidinone series (Scheme 1c). We hypothesized that a similar strategy could be used to synthesize various arylated polycyclic N-containing
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