Synthesis Of Pyrazino Research Articles

Synthesis of pyrazino[1,2-b]indazoles via cascade cyclization of indazole aldehydes with propargylic amines.

An efficient intermolecular annulation of indazole aldehydes with propargylic amines has been developed for the synthesis of pyrazinoindazoles under catalyst- and additive-free conditions. This straightforward methodology was found to feature a wide substrate scope, high atom economy and environmental advantages. The bioactivity results of these new pyrazino[1,2-b]indazoles showed that some of them exhibited significant antifungal activity.

Design, molecular docking and synthesis of pyrazino[1,2-a] indole derivatives via tandem Ugi-4CR/intramolecular cyclization as potential urease inhibitor agents

In the present paper, a novel series of pyrazino[1,2-a]indole derivatives 6(a-k) were synthesized by Ugi four-component reaction (U-4CR), followed by an intramolecular cyclization of the Ugi products in the presence of DBU as a catalyst, Subsequently, we assessed their inhibitory activity against Jack bean's urease enzyme in vitro, and some of these derivatives exhibited potent urease inhibition. Notably, compounds 6e (IC50 = 3.55 ± 1.11 µM), 6g (IC50 = 3.18 ± 0.42 µM), and 6j (IC50 = 3.80 ± 0.65 µM) demonstrated urease inhibitory effects comparable to the reference compound, thiourea. Additionally, our docking study corroborated these experimental results, confirming that the pyrazino[1,2-a]indole derivatives (6a-k) effectively interacted with the urease enzyme's active site, exhibiting proper binding energies and modes.

Three‐component one‐pot synthesis of pyrazino[2,3‐a]acridine derivatives under catalyst‐free conditions

AbstractA new series of pyrazino[2,3‐a]acridine derivatives were prepared, via three‐component reaction of quinoxalin‐6‐amine, aromatic aldehydes and 5,5‐dimethyl cyclohexane‐1,3‐dione or cyclohexane‐1,3‐dione in ethanol as a solvent at reflux. The advantages of this protocol include mild reaction conditions, easy purification, high yields, and catalyst‐free approach.

Use of Triethylsilane for Directed Enantioselective Reduction of Olefines: Synthesis of Pyrazino[2,1‐c][1,4]oxazine‐6,9‐diones with Full Control of the Absolute Configuration

Herein, we report the use of triethylsilane for the synthesis of hexahydropyrazino[2,1‐c][1,4]oxazine‐6,9‐diones with full control of three stereocenters. Unsaturated tetrahydropyrazino‐oxazine‐diones were prepared in accordance with a previously reported procedure and were treated with triethylsilane‐trifluoroacetic acid. The stereoselectivity of the reduction was completely dependent on the overall conformation of the oxazine scaffold, which was a consequence of the C9 configuration of the starting material. The results prove that triethylsilane can be used for directed enantioselective syntheses of single or fused morpholine‐based heterocycles.

Palladium-catalyzed double allylic alkylation of indole-2-hydroxamates: easy access to pyrazino[1,2- a]indole derivatives

The synthesis of pyrazino[1,2- a]indoles via a palladium-catalyzed double allylic alkylation of indole-2-hydroxamates is described. The reaction conditions are very mild and allow for a wide variety of substitutions on the indole core.

A Practical One‐Pot Procedure for the Synthesis of Pyrazino[2′,3′:4,5]thieno[3,2‐d]pyrimidinones by a Tandem aza‐Wittig/Heterocumulene‐Mediated Annulation Strategy.

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Intramolecular Cyclization of δ-Iminoacetylenes: A New Entry to Pyrazino[1,2-a]indoles

[reaction: see text] The synthesis of the pyrazino[1,2-a]indole nucleus was achieved by intramolecular cyclization of several 2-carbonyl-1-propargylindoles in the presence of ammonia. The reaction conditions were optimized using microwave heating and a pool of catalysts. Cyclization of 1-alkynylindole-2-carbaldehydes was easily accomplished under standard heating conditions, whereas microwave heating contributed to reduced reaction times and improved overall yields. Moreover, a fine-tuning of the microwave irradiation time made possible the selective synthesis of both pyrazino[1,2-a]indole isomers. TiCl4 proved the catalytic system of choice to achieve pyrazinoindoles in satisfactory yields starting from 1-alkynyl-2-acetylindoles and 1-alkynyl-2-benzoylindole derivatives. Also in these cases, microwave heating contributed to faster reactions and improved yields. The uncatalyzed versus catalyzed reaction mechanism is discussed.

ChemInform Abstract: Synthesis of Pyrazino(2,3‐c)isoquinolinecarboxylic Acids and Related Compounds.

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Synthesis of Pyrazino[2,3-c]isoquinolinecarboxylic Acids and Related Compounds

1-Methylisoquinoline-3,4-diamine has been synthesized and condensed with α-dicarbonyl compounds to give the fused pyrazine ring. Oxidation of methyl groups gives the 3- and 6-carboxylic acids. Nitration occurs in the benzenoid ring to give the single 10-nitro product, and formation of an unusual 6-trinitromethyl compound is also reported.

The synthesis of “stretched‐out” analogs of lumazine, 6,7‐dimethyllumazine and 2‐amino‐5,6,7,8‐tetrahydro‐6,7‐dimethyl‐4‐pteridinone

AbstractThe synthesis of pyrazino[2,3‐g]quinazolin‐2,4‐(1H,3H)dione (4) and its 7,8‐dimethyl derivative (5), as linear benzo‐separated lumazines, is reported. Also described is the preparation of 2‐amino‐6,7,8,9‐tetrahydro‐7,8‐dimethylpyrazino[2,3‐g]quinazolin‐4‐one (6), as a linear benzo‐separated analog of a synthetic cofactor for phenylalanine hydroxylase. All of the syntheses began with ethyl 2,4,5‐triaminobenzoate (8) and proceeded through the appropriate derivatives of ethyl 6‐aminoquinoxaline‐7‐carboxylate (9, 10, and 11) which were subsequently ring closed to 4, 5, and 6.

Folate antagonists. 14. Synthesis of pyrazino[2,3‐f]quinazoline‐8,10‐diamines and related heterocycles as potential antimalarial agents (1,2)

AbstractAmination of 5‐chloro‐6‐nitro‐2,4‐quinazolinediamine (2) afforded 6‐nitro‐2,4,5‐quinazolinetriamine (3) which was hydrogenated catalytically to produce 2,4,5,6‐quinazolinetetraamine (5). Condensation of 5 with the requisite diketones afforded 8,9,10,11‐tetrahydropyrimido[5,4‐a]‐phenazine‐1,3‐diamine (6), several pyrazino[2,3‐f]quinazoline‐8,10‐diamines (7–10,13) as well as two pyrimido[4,5‐f]phenazinediamines (11,12). Amination of 2 in the presence of formamide at 120° led to the formation of 9‐nitro‐1H‐pyrimido[4,5,6‐de]quinazolin‐5‐amine (4). None of these compounds showed suppressive activity when tested parenterally against lethal Plasmodium berghei infections in mice. When tested against various bacteria in vitro, 7 and 10 exhibited activity against Streptococcus faecalis at a concentration below 2.5 μg./ml.

The synthesis of pyrazino[2,3‐d]pyridazine and some of its derivatives

AbstractPyrazino[2,3‐d]pyridazine (I) was synthesized by two different routes. 5, 8‐Dihydroxy‐pyrazino[2, 3‐d]pyridazine (IV) was converted to 5, 8‐dichloropyrazino[2, 3‐d]pyridazine (V) and 5, 8‐dibromopyrazino[2, 3‐d]pyridazine (Va). When V was treated with various benzyl mercaptans and alkoxides the corresponding disubstituted derivatives were obtained. Compound V when allowed to react with aromatic amines gave 5, 8‐bisamino‐pyrazino[2,3‐d]pyridazines, however, with aliphatic amines only mono substituted products were obtained substituted in the 8‐position. The reaction of pyrazine‐2, 3‐dinitrile with hydrazine gave 5, 8‐diaminopyrazino[2, 3‐d]pyridazine (X).