Expanding the substitution pattern of 2(1H)-pyrazinones via Suzuki and Heck reactions

Transition metals in organic synthesis: Highlights for the year 2005

“…Heterocyclic ring-systems such as, bromo-oxabicyclo[3.2.1]octadienes [28], 6-bromoimidazo[1,2-a]pyridine [174], 3,5-dichloropyrimidine and 3,5-dichloropyridine [175], 4,7-dibromo-2,1,3-benzothiazole with a 3-indolylboronic acid [176], halo-amino-pyridines, pyrazines and pyrimidines [154], chloropyrazines in a synthesis of botryllazines [14], 4-chloroquinoline-2-one [177], 3-trifloxypyrazole [178], 8-bromo-2 -deoxyguanosine [179], 2-chloro-2 -deoxyinosine [180], 6-halopurines [30], 6-fluoro-, 6-(3-methylbutylsulfanyl)-, and 6-(3-methylsulfonyl)purine [181], 5-trifloxyindoles [29], 3-iodo-5-bromoindole [182], 4-bromobenzofuran [183], 5,7-dichloro-1,6-naphthyridin-2-(1H)-one [184], 7-bromo-pyrido [2,3-b]pyrazine [185], 5-iodo-1,2,3-triazoles [186], 3-bromo-2,5-dihydrofuran-2-one [187], 3-halo-indazoles [188,189], 3-chloro-2-pyrazolines and 3-chloro-1-phenyl-1,4,5,6-tetrahydropyridazine [190] and 3-iodo-4H-chromen-4-one [191] were used in Suzuki type cross-couplings. Regioselective coupling in the 4-position of 3-bromo-4-trifloxyquinolin-2(1H)-one [192], the 2-position of di-and tribrominated pyrroles [193] and the 3-position of 3,5-dichloropyrazin-2-ones [194] were reported. A regioselective coupling in the 2-position of 2,4-dibromopyridine was used in a synthesis of A2E [73].…”

“…Halides and triflates of heterocyclic ring systems, such as 3-bromoquinoline-2-ones [177] and 7-bromo-pyrido[2,3-b]pyrazine [185] were used in Heck reactions. Regioselective reaction in the 3-position of 3,5-dichloropyrazin-2-ones was reported [194].…”

Synthesis of N-Hydroxypyrazin-2(1H)-ones via Selective O-Debenzylation of 1-Benzyloxypyrazin-2(1H)-ones Using Flow Methodology

“…This explains their potential to inhibit specific metal-containing enzymes involved in human immunodeficiency virus [HIV] [2][3][4] and cancer progression (histone deacetylases [HDACs], mitochondrial membrane permeabilities [MMPs], ribonucleotide reductase [RNR]) [5][6][7]. Our group has previously been working on the design and synthesis of highly functionalized pyrazinones [8][9][10][11][12][13][14]. In the current paper, we focus on our newly developed synthesis of N-hydroxypyrazinones.…”

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

“…6,7 A lot of research in our group was directed towards the development of synthetic strategies for highly functionalized pyrazinones. [8][9][10][11][12][13][14][15] Since there are bioactive compounds known in nature containing an N-hydroxypyrazinone core (e.g., aspergillic acid, Fig. 1), [16][17][18] we focused our attention to the development of new strategies to synthesize pyrazinones containing 1-benzyloxy functionality.…”

“…Our synthetic scheme for the synthesis of 1-benzyloxypyrazin-2(1H)-ones improves upon reported procedures [19][20][21][22][23] and is similar to chemistry we already applied in the preparation of 1-alkyl/aryl pyrazinones. 11,12 It relies on the base catalysed condensation of a glyoxal derivative with an amino acid hydroxamate. The condensations with phenyl glyoxal and diacetyl need a higher reaction temperature (50-70°C) compared to those with glyoxal and methyl glyoxal.…”