Pyrazine analogues

The angular annelation of the pyridine and pyrazine rings in 28 have been confirmed by a large coupling constant (9 Hz), and this is believed to be attributable to oz/,4o-interaction of the protons. The same configurations on the 4-pyridone and pyrazine analogue 20 shows Vs 9 = 6Hz and Jz,3 = 1.8 Hz, respectively <2000M293>. 

A very recent report from a group at Burroughs-Wellcome details the only example of a monocyclic pyrazine analogue (338) of MTX Scheme 3.62)... 

The high 77-deficiency at C-7 is also apparent from the nucleophilic addition reaction with sodium borohydride selective formation of the 6,7-dihydro derivative (566) results with this reagent. The reaction may also proceed further by reductive loss of the 7-substitutent (76CPB235). In the pyrazine analogue (567) both LAH and sodium borohydride treatment lead to saturation of the pyrazine ring (78JOC341). 

Pjrazinamide is a pyrazine analogue of nicotinamide. It is bactericidal for Mycobacterium tuberculosis in an acid environment and within macrophages (1). Regimens that include pyrazinamide produce significantly more rapid rates of sputum conversion than any other combination. Pyrazinamide is therefore especially appropriate in the initial phase of treatment. In the 6-month... 

The known a-biomoesier 102 has been used to malm the imidazo(l,2-a]pyrazine analogue 103 of adenosine as outlined in Scheme 10, and the isothiazolo(4,5-d)pyritiiidine 104 and its a-... 

A computer search of volumes 70-95 of Chemical Abstracts using the keyword Pyrazine resulted in more than 2600 references, and, after removal of fused pyrazine systems and cross-referencing the remaining references, this number increased to approximately 7000 in total. When the benzopyrazines quinoxaline and phenazine were added the number of references was in excess of 10 000, all of which might be considered to be relevant to a chapter devoted to pyrazines and their benzo analogues. 

IR spectroscopy has also been used in structural problems in 2- and 3-hydroxypyrido[3,4-f ]pyrazines (63JCS5156), in 8-oxopyrido[2,3-f ]pyrazine-7-acids (73MI21501) and in the pyrido[3,4-f ]quinoxaline field (74JCS(P1)1965). IR spectra were recommended for the distinction of isomeric products in the Isay reaction (Section 2.15.15.6.1) (71TH21500) UV spectra were not satisfactory. The Raman spectra of a number of 1- and 3-deazaflavin analogues have been recorded and discussed (80BBA(623)77). 

The tautomerism of some deaza analogues of riboflavin has been studied (77TL2551). The tautomerism of 3-ethoxalylmethyl- and 3-acetonyl-pyrido[2,3-f ]pyrazin-2-ones is fully discussed in (71TH21500 p. 68)... 

In a series of reactions with potassium amide in liquid ammonia, 6-chloropyrido[2,3-f)]pyrazine gave reduction and ring contraction (Section 2.15.13.3), the 6-bromo analogue underwent only reduction, whilst the 6-fluoro derivative gave only the 6-amino substitution product (79JHC305). 

When thieno[2,3- ]pyrazine was chlorinated, the reaction resembled the corresponding pyridine and pyrimidine (152) analogues in that 13-substitution in the thiophene ring was observed (80JHC1019). 

In [l,2,4]triazolo[4,3-a]pyrazine (174) bromination took place at the 5-position rather than in the triazole ring (77JOC4197). It was not possible to convert the 3-hydroxy derivative into the 3-chloro analogue (68JHC485). The isomeric [1,5-a] compound (175) was also brominated at C-5 (74TL4539), whereas its 7-oxide gave the 8-chloro derivative under Meisenheimer conditions [80JCS(P1)506]. 

Nakano, M., Sugioka, K., Ushijima, Y., and Goto, T. (1986). Chemiluminescence probe with Cypridina luciferin analogue, 2-methyl-6-phenyl-3,7-dihydroimidazo[l,2-a]pyrazine-3-one, for estimating the ability of human granulocytes to generate superoxide anion. Anal. Biochem. 159 363-369. 

R.W. Millar, S.E. Philbin, R.P. Claridge, J. Hamid, Studies of novel heterocyclic insensitive high explosive compounds pyridines, pyrimidines, pyrazines and their bicyclic analogues . Propellants Explos. Pyrotech. 81—92. 

Millar and co-workers reported the synthesis of a number of energetic pyrimidines, pyrazines and their bicyclic analogues, including 2,5-diamino-3,6-dinitropyrazine (185) and the quina-zoline (186)." ... 

Aromatic 7c-systems bearing two positive charges can accept one electron to form a delocalised radical-cation, which is isoelectronic with the radical-anion from the corresponding aromatic hydrocarbon. The phenanthrene analogue 4 is one such example [30]. Pyrazine is bis-protonated and reduced in acid solution to the... 

The biologically active relatives of folic acid and biopterin are the tetrahydro compounds with a reduced pyrazine ring. Reduction to this level occurs rapidly in vivo. The corresponding electrochemical process is well illustrated by reduction of the N-methylated analogue 28 [95], Reduction to the 5,8-dihydro stage is a reversible two-electron and two-proton process. The product rapidly tautomerises to the... 

It should be noted that, as all carbon positions in pyrazine are identical, the locant 2- in a monosubstituted derivative is unnecessary. All possible reduced derivatives of pyrazine 1, and several of those of its benzo analogues quinoxaline 2 and phenazine 3, are known. There are four dihydropyrazines, the 1,2-, 2,3-, 1,4-, and 2,5-isomers, two tetrahydropyrazines, the 1,2,3,4- and 1,2,3,6-, and hexahydropyrazine or piperazine, the last of which is omitted in this chapter. The reduced quinoxalines are the 1,2- and 1,4-dihydro compounds and 1,2,3,4-tetrahydroquinoxaline. The only known reduced phenazine is 1,4-dihydrophenazine. Hydroxypyrazine 4 and hydroxyquinoxaline 6 have been shown to exist in the tautomeric amide form by spectral studies, and therefore they are formulated as 2(1//)-pyrazinone 5 and 2(l//)-quinoxalinone, respectively. In contrast, aminopyrazine and aminoquinoxaline exist as described in the amino rather than the imino forms (Figure 1). 

One of the very few reports in this area is an extension of work seen previously in the synthesis of pyrrolo[2,3-3]pyrazines. If the pyrazine 333 is permitted to react with activated methylene compounds bearing at least one a-carbonyl group, the oxygen analogue 334 is produced (Equation 119) instead of the nitrogen system (no yields given) <1998JCM284>. 

Hydrogenation of 3-methylpyrido[2,3- ]pyrazin-2(37/)-one 211 by the action of NaBH4 in NaOH gave 212 <1995JHC703>. On the other hand, the tetrahydro analogue 214 was obtained from 213 by the action of H2/ Raney-Ni in THF <1996JHC1737>. 

Condensation of 3-amino-2-(methylamino)pyridine 647 with diethyl 2-oxomalonate in boiling ethanol afforded 2-carbethoxy-4-methylpyrido[2,3- ]pyrazin-3(4//)-one 213 <1996JHC1737>. On the other hand, condensation of 647 with diethyl oxaloacetate gave ethyl [2(l//)-oxopyrido[2,3- ]pyrazine-3(4//)-ylidene]carboxylate 648 in addition to the formation of pyridodiazepine 649 as a by-product <1996JHC1737>. However, the condensation of 647 with diethyl 2-oxoadipate gave the 2-ethoxycarbonylpropyl analogue 650 (Scheme 30) <1994FA259>. 

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