Imidazo quinoxalines acidity

Monoacylation of 2,3-diaminoquinoxalines has been achieved by reaction with an acid anhydride in THF. Under more vigorous conditions reaction of 2,3-diaminoquinoxalines with acid anhydrides results in ring closure to an imidazo[ ]quinoxaline. Similar ring closures have been carried out with aldehydes, acyl halides, formic acid, orthoesters, and urea. Polycyclic compounds have also been prepared from 2,3-diaminoquinoxaline by reaction with 1,-2-dicarbonyl compounds and 1,2-diamines, as illustrated in Scheme 7. 

Two decades after the first example of annulation of the imidazole moiety (Nispen et al. 1980) to bond c of quinoxaline under the action of dilifhium salt 43, a new procedure has been suggested in which the initial compounds are quinoxali-nones 59 (Banish and Spergel 2001 Chen et al. 2001, 2002a Hazeldine et al. 2005). Protected iV-(4-methoxybenzyl)quinoxalinones 60 are introduced into the reaction with TsMIC in THF in the presence of NaH, which leads to imidazo-quinoxaline 61 in high, sometimes quantitative, yields. The protective group is removed under the action of trifluoroacetic acid (TFA), anisole and trifluoromethanesulfonic acid (TfOH). This method is simple and enables the... 

The reaction of l-(o-methylaminophenyl)imidazole-2,5-dione 101 with ethyl formate under the action of sodium yields 1,3-dioxoimidazoquinoxaline 102, which is reduced by tin in a mixture of acetic and hydrochloric acids to give imidazo-quinoxaline 103 (Scheme 4.46) (King and Clark-Lewis 1951). 

Quinoxalinediamine (172) and p-methoxybenzoic acid gave 2-p-methoxy-phenyl-17/-imidazo[4,5-/]quinoxaline (174) [neat synthon (2 equiv), 210°C,... 

A series of imidazo[l,5-a]quinoxaline amides, carbamates, and ureas which have high affinity for the y-aminobutyric acid A/benzodiazepine receptor complex was developed. Compounds within this class have varying activities ranging from antagonists to full agonists. However, most analogs were found to be partial agonists as indicated by [ S]TBPS and Cl current ratios. Many of these... 

From fried beef, another new compound, 2-amino-3,8-dimethy1-imidazo[4,5-/]quinoxaline (MelQx), was isolated, and its structure was confirmed by chemical synthesis (15). The structures of all the compounds isolated from pyrolysates of amino acids and a protein, and from cooked fish and meat, are shown in Table II. 

Some very clever syntheses of pyrazines were reported. Tandem Mn02-mediated oxidation followed by in situ trapping with aromatic or aliphatic 1,2-diamines was shown to give rise to quinoxalines, dihydropyrazines, pyrazines, and piperazines without the need to isolate highly reactive 1,2-dicarbonyl intermediates <03CC2286>. A new intramolecular cyclization route to highly substituted chiral 6,7-dihydro-5//-imidazo[l,5-a]pyrazin-8-ones like 157 from Meldrum s acid was developed <030L3907>, and 5-chloropyrido[3,4-6]pyrazines were prepared from 1,2-dicarbonyl compounds and 2-chloro-3,4-diaminopyridine <03H(60)925>. A synthesis of... 

Deleuze-Masquefa et al. [15] showed that the microwave assisted bimolecular condensation of 2-imidazole carboxylic acid, followed by coupling with ortho-fluoroaniline and subsequent substitution on imidazole ring by Suzuki cross-coupling reaction gave the imidazo[l,2-a]quinoxaline (xiii) analogues in good yields. All the synthesized compounds showed high activities when evaluated for antitumor activities. 

The aromatic ring system has been prepared both from quinoxaline intermediates and from 1-phenylimidazoles. Reaction of the 2-chloroquinoxalines 1 with aminoacetaldehyde dimethylacetal followed by acid treatment of the resultant aminoacetals gave imidazo[l,2-ajquinoxaline (2) and its 4-phenyl derivative (3). Compound 3 was the... 

Although the 1,3-diphenyl 2-oxo compound 63 is stable to acid hydrolysis, imidazo[4,5-h]quinoxaline itself undergoes very ready hydrolytic ring opening. Hot dilute hydrochloric acid gives 3-aminoquinoxalin-2-one (74), and hot alkali affords 2,3-diaminoquinoxaline (57). Similarly acid treatment of the 2-methyl N-oxides 72 and 73 provides the quinox-aline N-oxides 75 and 76, respectively. ... 

Dehydration of the aminobenzimidazoles 96 with polyphosphoric acid gave the cyclized products 97. ° Compound 98 has also been prepared by the same approach. Chloroethylbenzimidazoles such as 99 have been cyclized to imidazo[l,5,4-de]quinoxalines, ° and the bis(chloroethyl)-amine 101 was similarly cyclized to the quaternized heterocycle 102. ... 

Verma and collaborators reported selective syntheses of 4,5-dihydro-imidazo- and imidazo[l,5-a]quinoxalines via a modified Pictet-Spengler reaction by treating 2-imidazolyl anilines 134 with aromatic aldehydes in the presence ofp-toluenesulfonic acid in toluene (Scheme 66) (13TL5984). 

Jacobsen EJ, TenBrink RE, Stelzer LS, Belonga KL, Carter DB, Im HK, Im WB, Sethy VH, Tang AH, VonVoigdander PF, Petke JD (1996) High-affinity partial agonist imidazo[l,5- ] quinoxaline amides, carbamates, and ureas at the y-aminobutyric acid A/benzodiazepine receptor complex. J Med Chem 39(1) 158-175. doi 10.1021/jm940765f... 

Ager IR, Barnes AC, Danswan GW, Hairsine PW, Kay DP, Kennewell PD, Matharu SS, Miller P, Robson P, Rowlands DA, Tully WR, Westwood R (1988) Synthesis and oral antiallergic activity of carboxylic acids derived from imidazo[2,l-c][l,4]benzoxazines, imidazo[l,2-tj] quinolines, imidazo[l,2-a]quinoxalines, imidazo[l,2-a]quinoxalinones, pyirolo[l,2-tj]quinox-alinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,l-f>]benzothiazoles. J Med Chem 31 (6) 1098-1115. doi 10.1021/jm00401a009... 

Under the action of polyphosphoric acid (PPA), hydrazones 19a, b lose diphenylamine and convert into imidazo[l,5-a]quinoxalines 20a, b (Scheme 4.8) (Kollenz 1972). 

Heating l,4-bis(aroylmethyl)quinoxalin-2,3-diones 135a-j in acetic acid in the presence of ammonium acetate leads to 2-aryl-5-aroylmethylimidazo[l,2-a] quinoxaline-4-ones 136a-j (B3Q-type cyclization, see Fig. 4.6), whereas expected l,5-diarylbis(imidazo[l,2-a 2, r-c])quinoxalines 137 are not identified in the reaction mixture. Starting compounds 135 have been obtained by alkylation of quinoxalinediones 138a, b with aroylmethyl bromides (Scheme 4.61) (Hariharakrishnan et al. 2008). 

Elchaninov and Elchaninov 2014) reactions. The formation of 2-(lH-imidazo[4,5-Z7]pyridin-2-yl)-3-arylquinoxahnes 96a-d from pyrido[2,3-fe]pyrazin-2(lfl)-ones 95a-d and 1,2-DAB 5a proceeds in AcOH under reflux for 35-47 h. It should be noted, that carrying out the reaction with refluxed AcOH for 3 h leads to the formation of 2-amino-3-azaanylide quinoxaline 3-phenyl-2-carboxylic acids 97. This has been illustrated by the reaction of 2-(lH-imidazo[4,5-fc]pyridin-2-yl)-3-phenylquinoxahne 95a and 1,2-DAB 5a (Table 6.4) (Mamedov et al. 2010a). 

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