2-Chloro-3- pyrazine cyclization

Cyclization of (25)-2-(rerc-butoxycarbonylaminomethyl)-l-(2-chloro-acetyl)piperidine on the action of NaH in THF gave (9aS)-2-(rerc-butoxycarbonyl)perhydropyrido[l,2-a]pyrazin-4-one (99H(51)2065). 3-Benzyl-2,3,4,4 ,5,6-hexahydro-l//-pyrazino[l,2-a]quinolin-l-ones 413... 

Very few imidazo[4,5-b] pyrazines have been reported in the literature1-3 and no good general method has been available for preparing compounds in this most interesting heterocyclic class. We have found that the Curtius reaction of a 3-aminopyrazine-2-carboxylic acid azide (Scheme I) proceeds with intramolecular cyclization to provide, in good yield, a wide variety of the subject compounds. We will report here only the 6-substituted 5-chloro-l, 3-dihydro-2tf-... 

Chloro-3-hydrazinopyrazine (217) gave 2-chloro-3-[4-(ethoxycarbonylmethyl)-(thiosemicarbazido)]pyrazine (218) (Et02CCH2NCS, CHC13, reflux, 1 h 63%), which underwent cyclization with loss of HC1 to afford 3-ethoxycar-... 

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... 

Various bicyclic heterocycles have been prepared from carbamoylpyrazine V-oxides 2-amino-5-chloro-3-7V-methyIcarbamoylpyrazine 1-oxide refluxed with triethyl orthoformate and acetic anhydride gave 6-chloro-3-methyl-4-oxo-3,4-dihydropteridine 8-oxide (1222) 2-amino-3-carbamoyl-5-methyl(or phenyl)pyrazine 1-oxide with triethyl orthoformate, or with ethyl chloroformate followed by cyclization of the intermediate urethane, gave 6-methyl(or phenyl)-4-hydroxy-pteridine 8-oxide (537). 

A regioselective synthesis of alkylpyrazines (155) starts with condensation of a-oximino carbonyl compounds with allylamines (Scheme 38). The imine intermediates are isomerized in the presence of potassium r-butoxide to the corresponding 1-hydroxy-1,4-diazahexatrienes. Thermal cyclization-aromatization to pyrazines is best performed after 0-acylation of the oximes with methyl chloro-formate <91JOC2605>. 

Treatment of 2-(2-hydroxyethylamino)pyrazine (40) with thionyl chloride, followed by cyclization of the resultant chloro compound in boiling ethanol, gave a considerable amount of tar together with 6.5% of the 2,3-dihydroimidazo compound (41). The 5,6-diphenyl analogue of 41 has been similarly prepared in undisclosed yield. The tetrahydro derivative 44 was obtained when the tetrahydropyrazine 42 was heated in ethanolic hydrochloric acid with a-amino-a-cyanoacetamide (43). " ... 

Condensation of 6-chloro-3,5-dicyano-2-(dimethylamino)methylenelami-nolpyrazine with a-mercaptoacetate or l-mercapto-2-propanone introduces C-S bond formation between the C7 of the pyrazine ring, forming 41, which can then be cyclized under basic conditions. 

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