8- Fluoro-2 -quinoxalinone

Bromo-7-fluoro-3,4-dihydro-2(177)-quinoxalinone (35) gave 6-bromo-7-fluoro-5-nitro-2,3(177,477)-quinoxalinedione (36) regioselectively (fuming HNO3, F3CCO2H, 20°C, 12 h 85% analogs likewise). ... 

Fluoro-2(17/)-quinoxalinone 4-oxide (273) gave 6-fluoro-3-methyl-2(l//)-quinoxalinone (275), probably by degradation of the adduct (274) (ACCH2-COjEt, PhH, H2O, NaOH, 65°C, 1 h % several analogs likewise). ... 

Bromo-7-fluoro-3,4-dihydro-2(l//)-quinoxalinone (2) gave only 6-bromo-... 

A second side reaction suffered by Ar(4)-unfunctionalized quinoxali-nones leading to racemization at the a-carbon was revealed in the closely related studies of Morales and co-workers, who assembled the [6,6] ring system from 4-fluoro-3-nitrobenzoic acid coupled as an ester to Wang resin (lb) (Scheme 12).9 This undesirable side reaction could also be prevented by functionalization of iV(4) prior to cleavage, which in this instance was accomplished by acylation with chloroformates and thiochloroformates. Derivatization at (V(l) was again effected using the Ellman alkylation protocol and provided optically pure samples of the quinoxalinones (72). 

Cheng-Ting et al. [13] developed a simple and efficient method for the synthesis of benzimidazole linked quinoxalinones (i) on soluble polymer support using microwave conditions. The key steps involved in the implemented linear synthesis are the acid catalyzed condensation of 4-fluoro-3-nitrobenzoic acid with polymer... 

As shown in Scheme 23, solid-phase-bound Fmoc-protected amino acids 82 are deprotected and coupled with 4-fluoro-3-nitrobenzoic acid. The acid moiety of 83 is converted to the amide 84, and reduction of the nitro group with SnCU 2112O initiates cyclative cleavage to 85 after aqueous work-up. This synthesis gives two points of diversification, which can be increased by an alkylation step in solution to give 86. Additionally, the authors oxidized the heterocychc core 85 with p-chloranil to give the corresponding quinoxalinones (not shovm) [38]. 

Tseng and colleagues [58] reported a three-step synthesis of fused tetrahydro-P-carbolinequinoxalinones, solely based on the use of ionic liquids as solvents. Tetrahydro-P-carboline is a central core for many biologically important indole alkaloids, and the moiety of quinoxalinone often exhibits a wide spectrum of biological activities such as being anti-HIV, antihypertensive, and a ligand for a number of protein receptors. As a first step, tryptophan methyl ester was reacted with an aldehyde to form tetrahydro-p-carboline by Pictet-Spengler cyclization that further reacted with l-fluoro-2-nitrobenzene to form iV-aryl-tetrahydro-P-carboline. Intramolecular cyclization upon a reduction reaction in step three provided the desired tetrahydro-P-carbolinequinoxalinones. The entire process was based on the use of 1-n-butyl-... 

The efficiency of an Ugi/de-Boc/cycUzation strategy for constmction of heterocy-chc compounds has been improved through the incorporation of MW and fluorous technologies. In the synthesis of substimted quinoxalinones and benzimidazoles, a flnorous-Boc-protected diamine is employed for the Ugi reactions. Both the Ugi and the post-condensation reaction proceed rapidly under MW irradiation and the reaction mixtures are purified by solid-phase extraction (SPE) over fluoro flash cartridges (Scheme 3.42) [102]. 

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