The synthesis of some polycyclic N-H acids with quinoxaline and [1,2,4]triazines 1

3-(4-Aminophenyl)-1,2-dihydro-quinoxaline-2-one ( 2b ), 3-(2-aminophenyl)-6,7-dimethyl-1,2-dihydro-quinoxaline-2-one ( 1b ), its 3-(4-aminophenyl)-isomer ( 3b ), 3-(2-aminobenzyl)-1,2-dihydro-quinoxaline-2-one ( 4b ), its 3-(4-aminobenzyl)-isomer ( 6b ), 3-(2-aminobenzyl)-6,7-dimethyl-1,2-dihydro-quinoxaline-2-one ( 5b ) and its 3-(4-aminobenzyl)-isomer ( 7b ) were diazotised and the resulting diazonium salts were coupled with ethyl cyanoacetylcarbamate, 3-methyl-1,2-dihydro-quinoxaline-2-one, 3,6,7-trimethyl-1,2-dihydro-quinoxaline-2-one and 3-methyl-6,7-dichloro-1,2-dihydro-quinoxaline-2-one.


Introduction
Neurological diseases such as Creutsfeldt-Jacob disease, bovine spongiform encephalopathy and scrapie are caused by induced conformational changes of a normal host protein designated as PrP c to an abnormally folded protein designated as PrP Sc .Compounds which can affect the conformation of the protein chain could be helpful in treatment of such diseases.The newly discovered anti-prion compounds can be grouped into branched polyamines or rigid condensed heterocycles with tetrapyrrole or acridine skeletons 2 .Also, some non-condensed polyatomic heterocyclic compounds in which free rotation of individual cycles can offer several conformations could be suitable in controlling conformations of the protein chain.Such molecules can adapt themselves to the spatial arrangement of a certain part of the protein chain but, at the same time, due to bonding and non-bonding interactions they can change the conformation of this chain.

Experimental Section
3-(4-Aminophenyl)-6,7-dimethyl-1,2-dihydroquinoxaline-2-one (3b).A mixture of acetyl derivative (3c) (3.89 g; 12.66 mmole) and a solution of KOH (6.5 g) in a mixture of ethanol (30 ml) and water (25 ml) was heated until a solution formed.The solution was then refluxed for 5 hours.The ethanol was evaporated from the reaction mixture by heating on a water bath and the solution was acidified with acetic acid to pH 5. The next day, a yellow crystalline compound was collected with suction, washed with water and dried in air.For further details see tables 1-3 in the supplementary material section.

3-(2-Aminobenzyl)-6,7-dimethyl-1,2-dihydroquinoxaline-2-one (5b).
To solution of FeSO 4 .7H 2 O (1.39 g; 5.0 mmole) in water (7 ml) was added to a solution of Ba(OH) 2 .8H 2 O in hot water (15 ml).The mixture of Fe(OH) 2 and BaSO 4 was quickly collected with suction and washed with hot ethanol.The mixture was added to a solution of 3-(2-nitrobenzyl)-6,7-dimethyl-1,2dihydroquinoxaline-2-one (5a) (154,66 mg; 5,0 mmol) in hot ethanol (60 ml).The reaction mixture was refluxed for 90 minutes on a water bath and then filtered with suction and washed with hot ethanol.The filtrate was evaporated and the solution was mixed with a little water.The product was collected with suction, washed with water and dried in air.For further details see tables 1-3 in the supplementary material section.

General procedure of the synthesis of 1,2-dihydro-quinoxaline-2-ones substituted in position 3 (1d-7d, 1e-7e, 1f-7f, 1g-7g)
A solution of NaNO 2 (140.0;2.0 mmole) in ice-cold water (4 ml) was added portionwise under stirring to a solution (2.02 mmole) of the corresponding aromatic amine 2b-8b in a mixture of hydrochloric acid (37 %, 3.0 ml) and water (10-30 ml), which was cooled in an ice-bath.The solution was left to stand for 30-60 min and then was added portionwise during 10 min to a stirred mixture obtained by dissolving the following compounds as stated below.
In each case, the next day, a crystalline compound was collected with suction, washed with water and dried in air.
The next day, the reaction mixture was diluted with water and the next day, crystalline compound was collected with suction, washed with water and dried in air.
The data for these compounds are outlined in tables 1-3 in the supplementary material section.A mixture of hydrazone (1d) (0.432 g; 1.0 mmole), Na 2 CO 3 (120.0mg) and water (10 ml) was heated on a boiling water bath until a solution was formed and then for an additional 15 minutes.The solution was then allowed to cool and acidified with hydrochloric acid (37 %) to pH 1.After several hours, the crystalline solid was collected by suction, washed with a little water and dried in air.Compounds (3h), (5h) and (7h) were prepared by analogy to (1h) from hydrazones (3d), (5d) and (7d).
For further details see tables 1-3 in the supplementary material section.Melting points (Boetius) were not corrected.Infrared spectra were measured as potassium bromide disks and scanned on an ATI Unicam Genesis FTIR instrument.The NMR spectra were measured in DMSO-d 6 solutions on a Bruker AMX-360 spectrometer (360 MHz) with TMS as an internal standard.Elemental analyses were performed using an EA 1108 Elemental Analyzer (Fison Instrument).