Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• pyrrole esters is described. Efficient routes towards the synthesis of pyrrolopyrazinone, pyrrolotriazinone and pyrrolooxazinone have been developed. First, N-alkyne-substituted pyrrole ester derivatives were synthesized. Introduction of various substituents into the alkyne functionality was accomplished

• , cyclization of N-alkyne-substituted methyl 1H-pyrrole-2-carboxylates with iodine only resulted in the formation of the 6-endo-dig cyclization product regardless of the substitution of the alkyne functionality. Keywords: alkyne cyclization; pyrrole; pyrrolooxazinone; pyrrolopyrazinone; pyrrolotriazinone

• ][18][19][20][21][22]. In this article, we demonstrate for the first time the concept of the cyclization of N-alkyne-substituted pyrrole esters 7 (Figure 3) to provide a practical access to design pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone derivatives. Results and Discussion The

Synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones: Rearrangement of pyrrolo[1,2-d][1,3,4]oxadiazines and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles

• Kkonnip Son and
• Seong Jun Park

Beilstein J. Org. Chem. 2016, 12, 1780–1787, doi:10.3762/bjoc.12.168

• considered to be more facile and practical than previously reported procedures. Keywords: intramolecular cyclization; pyrrolooxadiazines; pyrrolotriazinone; rearrangement; Introduction Pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones have been considered to be biologically active compounds. For example, these

• and temperatures (entries 4–6, Table 1). Although initial attempts to synthesize pyrrolotriazinone 12a regioselectively were not successful, it should be highlighted that the regioisomers oxadiazine 11a and triazinone 12a could be easily prepared under very mild conditions (0 °C for 5 min), whereas

• rearrangement reaction of pyrrolooxadiazine 11a to pyrrolotriazinone 12a was explored (Table 2). For nucleophile-induced cyclization, pyrrolidine, Li(Me3AlSPh) [22], NaSMe, and NaOMe were assessed. Attempting the Mazurciewitcz–Ganesan procedure [23], using pyrrolidine as a nucleophile, was not successful (entry

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• worked well. As seen above, avoiding detrimental exotherms in scale up campaigns is a common reason for developing a continuous flow process. This approach is also demonstrated in the synthesis of the pyrrolotriazinone 73 via a exothermic oxidative rearrangement from 75, a key intermediate towards