Synthesis and properties of pyrrolo[1,2-a]pyrazines (review)

Pyrrolodiazines. 6. Palladium-Catalyzed Arylation, Heteroarylation, and Amination of 3,4-Dihydropyrrolo[1,2-a]pyrazines

“…The core structure of pyrrolodiazine 1 is present in a variety of biologically active molecules including some natural alkaloids such as hinckdentine and the variolin family (Figure ). In simple derivatives, the activity is strongly associated with the tetrahydro form of the diazine moiety.…”

“…In simple derivatives, the activity is strongly associated with the tetrahydro form of the diazine moiety. For example, 1,2,3,4-tetrahydropyrrolo[1,2- a ]pyrazine derivatives 2 exhibit antihypertensive, ischemic, anxiolytic, and equistomicidal activities. 1b, To date, compounds with the core structure 2 have been prepared from the corresponding fully oxidized precursors or from the corresponding dihydro derivatives by standard reduction procedures 1 Structures of some natural alkaloids containing a pyrrolodiazine core. …”

“…In connection with our recent studies on the chemistry and biology of pyrrolodiazines, we needed to develop a practical route to pyrrolo[1,2- a ]pyrazine derivatives 6 and this would involve the prior preparation of 5 . Most of the reported methods for the synthesis of 1-substituted 3,4-dihydropyrrolo[1,2- a ]pyrazines 5 are based on the condensation reaction between appropriately substituted furans or tetrahydrofurans and 1,2-diamino compounds to give 1-(2-aminoethyl)pyrroles 3 1e. Compounds 3 were reacted with carboxylic acids to afford the amides 4 , which are transformed into 5 under acid conditions (Scheme ).…”

Domino Approach for the Synthesis of Pyrrolo[1,2-α]pyrazine from Vinyl Azides

“…Some pyrrolo[1,2-α]pyrazine derivatives exhibit neuroleptic and cardiovascular activity. , The range of physiological activities has led to an array of synthetic procedures for the preparation of pyrrolo[1,2-α]pyrazine. Over the past decades, some of the most common synthetic methodologies reported in the literature include TiCl 4 -stereoselective 6-exo-dig cyclization of 2-acetyl- N -propargylpyrrole, POCl 3 -catalyzed condensation of pyrrolacetal, oxidation of the 3,4-dihydropyrrolo[1,2-a]pyrazine, and direct derivation of the parent pyrazine . However, some of the common synthetic approaches are limited by either their low yields, harsh experimental conditions, or substrate complexity.…”