Pyrrolo pyrazin-1 -ones

H,3H- Pyrrolo[l, 2-c]oxazole-l, 3-dione, 5,6,7,8-tetrahydro-IR spectra, 6, 978 [2.2](2,5)Pyrrolophane, N-aryl-rearrangements, 4, 209 Pyrrolophanes natural products, 7, 764 synthesis, 7, 771 Pyrrolophanes, N-aryl-synthesis, 7, 774 (2,4)Pyrrolophanes synthesis, 7, 771 Pyrrolo[3,4-c]pyran-4-ones synthesis, 4, 288 Pyrrolopyrans synthesis, 4, 525, 526 Pyrrolopyrazines synthesis, 4, 526 Pyrrolo[l, 2-a]pyrazines synthesis, 4, 516 Pyrrolo[2,3-6]pyrazines Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolo[3,4-c]pyrazole, 1,3a,6,6a-tetrahydro-structure, 6, 976 synthesis, 6, 1019 Pyrrolopyrazoles synthesis, 5, 164 Pyrrolo[l,2-6]pyrazoles synthesis, 6, 1002, 1006 Pyrrolo[3,4-c]pyrazoles reactions, 6, 1034 synthesis, 6, 989, 1043 Pyrrolo[3,4-c]pyrazolones synthesis, 6, 989 Pyrfolopyridazines synthesis, 4, 517 Pyrrolo[l, 2-6]pyridazines synthesis, 4, 297 6/7-Pyrrolo[2,3-d]pyridazines synthesis, 4, 291 2/f-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291 6/7-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291... 

One interesting example of this type of synthesis has been reported. 6-Phenyl-5//-5,7(6F/)-pyrrolo[3,4-/>]pyrazine (515) underwent electrolytic reduction in the presence of chlorotrimethylsilane to give the (unisolated ) substrate (516) that reacted with methyl acrylate (minimal detail) to afford a mixture of methyl 8-anilino-5-oxo-l,5-dihydro-6-quinoxalinecarboxylate (517) and methyl 5-ani-lino-8-oxo-4,8-dihydro-6-quinoxalinecarboxylate (517a) (17% and 21%, respectively, after separation). 

Besides furo[2,3-d]pyrimidines, 6-substituted 5H-pyrrolo[2,3-h]pyrazines have also been obtained in a microwave-promoted one-pot process starting from N-mesyl protected 2-amino-3-chloropyrazine (Scheme 60) [74]. The... 

All of the synthetic approaches to the pyrrolo[2,3-/ ]pyrazines originate with a suitably substituted pyrazine. Furthermore, all but one of these approaches have a chloropyrazine as the initial precursor. 

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>. 

The reaction of 2-(3-chloropyrazin-2-yl)-Tphenylbutan-l-one with either primary amines or hydrazines, catalyzed by acid, at high temperatures provided the corresponding pyrrolo[2,3- ]pyrazine <2006T9919>. 

Reaction of l-(3,4-dimethoxybenzyl)-9-hydroxy-l,2,3,4-tetrahydro-8//-pyrido[l,2-a]pyrazin-8-one with 37% formaldehyde solution gave a tetracyclic tetrahydroprotoberberine analogue in a Mannich-type reaction (78AJC187). Reactions of 2,3,4,4a,5,6-hexahydro-l//-pyrazino[l,2-a]-quinolines with 1 W-pyrrolo[2,3-h]pyridine in the presence of 37% aqueous CH20 and AcONa in AcOH, and with 3-dimethylaminomethyl-l //-pyrrolo[2,3-h]pyridine afforded 3-[(l//-pyrrolo[2,3-h]pyridin-3-yl)methyl] derivatives (94MIP6 96USP5576319). 

One report of the synthesis of pyrrolo[2,3-Z>]pyrazines from a pyrrole precursor has appeared. 2,3-Diiminopyrroles (178) have been cyclized to provide the tetraphenyl product (179) (Equation (61)) <88CB271>. 

An interesting pyrazine ring formation was detected between 5,6-diamino-1,3-dimethyluracil (309) and 6-hydroxy-6-(2,3,5-tri-0-benzoyl-/ -D-ribofuranosyl)-2//-pyran-3(6//)-one (310) leading to a mixture of l,3-dimethyl-7-(2,3,5-tri-0-benzoyl-/ -D-ribofuranosyl)lumazine (311), 1,3-dimethyl-6-[3-(2,3,5-tri-0-benzoyl-/ -D-ribofuranosyl)-3-oxopropyl]-lumazine (312), and 6,8-dimethyl-l-(2,3,5-tri-0-behzoyl-/ -D-ribofuranosyl)pyrrolo[l,2-/]pteridine-7,9-dione (313) (Equation (14)) <89JOC3927>. 

Depending on the reaction conditions, pyrrole amide 45 cyclizes either to pyrrolo[l,2- z]pyrazin-l-ones (46) or to a mixture of pyrrolo[2,3-c]pyridin-7-ones (47) and pyrrolo[3,2-c]pyridin-4-ones (48) [42], Isomers 47 and 48 are distinguishable by the lower chemical shift of the N—H proton (10.21 ppm) for 47 syn to the carbonyl) relative to that observed for 48 (9.08 ppm) and other spectral data. The cyclization leading to 47-48 is proposed to involve spiro intermediate 49. 

Some synthetic approaches to pyrazines relied on metal-assisted reactions. A synthesis of 6-substituted 5H-pyrrolol2,3-bJpyrazines via Pd-catalyzed heteroannulation from W-(3-chloropyrazin-2-yl)methanesulfonamide and alkynes was developed <04TL8087>, and 3- and 5-substituted 2(l//)-pyrazinones were prepared by Suzuki and Heck reactions using 3,5-dichloro-2(l//)-pyrazinones <04TL1885>. An improved synthesis of 6-substituted-5//-pyrrolo 2,3-iiJ-pyrazines via microwave-assisted Pd-catalyzed heteroannulation was developed <04TL8631>, and the reaction of a-diazo-P-keto esters with Boc amino acid amides in the presence of a Rh catalyst gave, after air oxidation, pyrazin-6-ones 111, which were then converted into tetrasubstituted pyrazines 112 <04OL4627>. 

Two examples have been reported of rearrangements that lead to pyrrolo[l,2-a]pyrazines. The Schmidt reaction on the ketone 52 gave only one product, the 3-oxo compound 53, paralleling the behavior of the ketone 54, which gave only the corresponding 3-oxopyrido[l,2-a]pyrazine on treatment with hydrazoic acid. The 1,6-dioxo compound 56 was obtained on refluxing the fused imidazoline 55 in water. 

The past year has seen the publication of Comprehensive Organic Chemistry, one volume of which contains much information on the six-membered ring systems to be reviewed in this article a monograph on the chemistry of condensed pyrazines has also appeared. Reviews on 1,4-thiazines, l,3-benzothiazines," pyridazines, benzo[c]cinnolines, quinazolines, purines, pyrrolo[3,2-c]quino-lines, 1,10-phenanthroline and its complexes, polyaza-phenanthrenes, and 1,9- and 1,10-diaza-anthracenes have been published. Other specialist reviews are devoted to catalytic methods of obtaining pyridine bases pyridine N-oxides the stereochemistry of quinolizines, indolizines, and pyrrolizines benzothiazinone dioxides 2-quinazolones and their cyclic homologues (e.g. 

A solid-supported carbonate reagent was used to initiate the formation of 2H-l,4-benzoxazin-2-ones 303 from P-nitroacrylate 301 and 2-aminophenol 302 (Scheme 7.72) [154]. This hetero-Michael addition/intramolecular transesteri-fication/elimination of HN03/[l,3]-proton shift domino reaction proceeded in moderate to excellent yields. In another study, a series of various functionalized pyrrolo[l,2-r]pyrazines 305 were made synthetically available through the reaction of vinyl azides 304 and lH-2-pyrrolecarbaldehyde (Scheme 7.73). The deprotonated pyrrole initially reacts in a Michael manner with the vinyl azides, with nitrogen as... 

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