Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• minor diastereomeric product through an exo-cycloaddition. One-pot synthesis of triazolobenzodiazepines Other than the multicomponent double cycloaddition reactions shown in the last section, we also utilized the first cycloaddition products for post-condensation reactions to generate new heterocyclic

• scaffolds. α-Substituted amino acids, such as 2-aminoisobutyric acid, could be used to block the second cycloaddition. Shown in Scheme 12 is a method development for the stepwise synthesis of triazolobenzodiazepines. The reaction of 2-azidobenzaldehyde, 2-aminoisobutyric acid and N-ethylmaleimide in MeCN

• for 6 h to afford the monocycloaddition compounds. Without isolation, the reaction mixtures were then used for the N-propargylation in the presence of K2CO3 under microwave heating at 110 °C for 1 h to give triazolobenzodiazepines 21a–f in 35–65% yields with 2:1 to 7:1 dr (Scheme 13). Other than 2

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkynes. Keywords: click chemistry; microwave chemistry; multicomponent reactions; triazolobenzodiazepines; Ugi reaction; Introduction Benzannulated heterocycles are among the most important

• of 1,2,4-triazolobenzodiazepines is the treatment of central nervous system (CNS) disorders. Such drugs as alprazolam and estazolam are used as anxiolytic agents, whereas adinazolam is known as an antidepressant [3]. Benzodiazepine molecules are ligands for GABA-receptors and act as positive

• receptor (CCK1R) located in the gastrointestinal tract. It is a potential target for treating obesity and diabetes [5]. Although derivatives of 1,2,3-triazolobenzodiazepines are less studied as to their 1,2,4-triazole fused analogs, 1,2,3-triazolobenzodiazepinone A (Figure 2) has already reached clinical

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• , triazolobenzodiazepines and tetrahydrochromeno[3,4-b]pyrrolizine (Scheme 2) [30][31][32][33][34][35][36][37][38][39]. Many of these scaffolds were synthesized through the combination of MCR and one-pot synthesis. A literature search indicated that a [3 + 2] cycloaddition-initiated method has also been used for the

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• , good flexibility in terms of substitution, and an unprecedented fusion pattern of the produced heterocycles. In view of the fact that the constructed 1,2,4-triazolobenzodiazepines represent a class of N-containing fused heterocycles with a new type of scaffold that is biologically interesting, the

• present synthetic protocol paves the way for further applications in drug-discovery research. Examples of marketed pharmaceutical 1,2,4-triazolobenzodiazepines. Crystal structure of salt 10k. The displacement ellipsoids are drawn at the 30% probability level. Crystal structure of the free base 13e. The

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• the synthesis of hydantoin-fused triazolobenzodiazepines starting from the Ugi reaction of o-azidobenzaldehyde (1a), propargylamine (2a), trichloroacetic acid (9) and benzyl isocyanide (4a, Scheme 5). The Ugi adduct was subjected to base-induced ring closing with NaOEt in EtOH which furnished the

• . The structure of hydantoin-fused triazolobenzodiazepine was confirmed by a X-ray crystal structure determination of 10a (Figure 3). The three-step synthesis of heterocycle-fused triazolobenzodiazepines involves the well-known Ugi 4-CR as the first step and the IAAC as the last, the mechanisms of which

• , we have developed a sequential synthetic strategy to access diketopiperazine-fused triazolobenzodiazepines from simple starting materials. It is noteworthy to mention that halogenated (chloro and bromo) benzodiazepines could be synthesized following the developed protocol which might show analogues