RESUMO
A method for the preparation of highly functionalized 4-iodo-7-azaindazoles is reported. These valuable heterocycles are synthesized via condensation of 2-hydrazineylpyrimidines with various iodoalkynones followed by Diels-Alder/retro-Diels-Alder cyclization. The method is general to the formation of products with a variety of C3, C5, and C6 substituents while preserving the C4 iodide functional handle for further late-stage functionalization. The utility of this transformation is demonstrated through the rapid synthesis of several bioactive azaindazole targets.
RESUMO
We report a diastereoselective, photocatalyst-free decarboxylative alkylation of (hetero)aryl sulfinimines using redox-active esters under blue light. High yields and diastereoselectivities can be achieved under mild conditions, and we demonstrate its utility as a synthetic method, especially for medicinal chemists.
Assuntos
Iminas , Catálise , Estrutura Molecular , AlquilaçãoRESUMO
We describe practical methods to prepare DOTAGA-DBCO and DFO-DBCO from commercially available starting materials. DOTAGA-DBCO is available in five steps from cyclen with a 33 % overall yield at gram scale. Our synthesis of DFO-DBCO also proceeds in five steps from commercially available starting materials. These bifunctional molecules possess chelating functionality for the binding of medically important radiometals and a strained alkyne suitable for Huisgen cyclization with an azide. These syntheses represent an important step toward improved radioimmunoconjugates for imaging and therapeutic applications.
Assuntos
Ciclamos , Imunoconjugados , Alcinos/química , Azidas/química , Ciclização , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêuticoRESUMO
Herein a method for the radical alkylation of heteroaryl halides that relies upon the combination of photoredox and nickel catalysis is described. The use of aliphatic N-(acyloxy)phthalimides as redox-active esters affords primary and secondary radicals for the decarboxylative dual cross-coupling with pyrimidine and pyridine heteroaryl chlorides, bromides, and iodides. The method provides an additional synthetic tool for the incorporation of medicinally relevant heterocyclic motifs.
Assuntos
Ésteres , Níquel , Alquilação , Estrutura Molecular , Oxirredução , Processos FotoquímicosRESUMO
A POCl(3)-mediated, direct amination reaction of heterocyclic amides/ureas with NH-heterocycles or N-substituted anilines is described. Compared to the existing methods, this operationally simple protocol provides unique reactivity and functional group compatibility because of the metal-free, acidic reaction conditions. The yields are generally excellent.
Assuntos
Amidas/química , Química Farmacêutica/métodos , Compostos Heterocíclicos/síntese química , Medicamentos sob Prescrição/síntese química , Ureia/química , Aminação , Compostos de Anilina/química , Anticolesterolemiantes/análise , Anticolesterolemiantes/química , Compostos Azabicíclicos/análise , Compostos Azabicíclicos/química , Benzamidas , Catálise , Cloridrato de Erlotinib , Zopiclona , Fluorbenzenos/análise , Fluorbenzenos/química , Compostos Heterocíclicos/análise , Humanos , Concentração de Íons de Hidrogênio , Hipnóticos e Sedativos/análise , Hipnóticos e Sedativos/química , Hipoglicemiantes/análise , Hipoglicemiantes/química , Mesilato de Imatinib , Estrutura Molecular , Compostos de Fósforo/química , Piperazinas/análise , Piperazinas/química , Medicamentos sob Prescrição/análise , Inibidores de Proteínas Quinases/análise , Inibidores de Proteínas Quinases/química , Pirimidinas/análise , Pirimidinas/química , Quinazolinas/análise , Quinazolinas/química , Rosiglitazona , Rosuvastatina Cálcica , Sulfonamidas/análise , Sulfonamidas/química , Tiazolidinedionas/análise , Tiazolidinedionas/química , Ureia/análogos & derivadosRESUMO
In our pursuit of an efficient, protecting-group-free synthesis of the dual CCK1/CCK2 receptor antagonist 1, we have developed chemoselective conditions for sulfonamide formation reaction in pure water and a PhNMe(2) mediated carboxamide formation, both in the presence of a carboxylic acid. Practical synthesis of an unnatural, chiral ß-aryl-α-amino acid is also described.
Assuntos
Receptor de Colecistocinina A/antagonistas & inibidores , Receptor de Colecistocinina B/antagonistas & inibidores , Estrutura Molecular , EstereoisomerismoRESUMO
A novel intramolecular 1,3-dipolar cycloaddition strategy for a rapid entry into benzofuropyrazoles is described. In a three-step sequence, (E)-2-(1,2-dichlorovinyloxy)aryldiazomethanes were generated in situ from the corresponding salicylaldehydes. Intramolecular cycloaddition followed by dehydrohalogenation garnered 3-chlorobenzofuropyrazoles in excellent yields. By careful choice of solvent, base, and reaction conditions, the entire sequence can be carried out in a one-pot procedure.