ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Imines , Catalysis , Molecular Structure , AlkylationABSTRACT
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.
Subject(s)
Cyclams , Immunoconjugates , Alkynes/chemistry , Azides/chemistry , Cyclization , Immunoconjugates/pharmacology , Immunoconjugates/therapeutic useABSTRACT
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.
Subject(s)
Esters , Nickel , Alkylation , Molecular Structure , Oxidation-Reduction , Photochemical ProcessesABSTRACT
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.
Subject(s)
Amides/chemistry , Chemistry, Pharmaceutical/methods , Heterocyclic Compounds/chemical synthesis , Prescription Drugs/chemical synthesis , Urea/chemistry , Amination , Aniline Compounds/chemistry , Anticholesteremic Agents/analysis , Anticholesteremic Agents/chemistry , Azabicyclo Compounds/analysis , Azabicyclo Compounds/chemistry , Benzamides , Catalysis , Erlotinib Hydrochloride , Eszopiclone , Fluorobenzenes/analysis , Fluorobenzenes/chemistry , Heterocyclic Compounds/analysis , Humans , Hydrogen-Ion Concentration , Hypnotics and Sedatives/analysis , Hypnotics and Sedatives/chemistry , Hypoglycemic Agents/analysis , Hypoglycemic Agents/chemistry , Imatinib Mesylate , Molecular Structure , Phosphorus Compounds/chemistry , Piperazines/analysis , Piperazines/chemistry , Prescription Drugs/analysis , Protein Kinase Inhibitors/analysis , Protein Kinase Inhibitors/chemistry , Pyrimidines/analysis , Pyrimidines/chemistry , Quinazolines/analysis , Quinazolines/chemistry , Rosiglitazone , Rosuvastatin Calcium , Sulfonamides/analysis , Sulfonamides/chemistry , Thiazolidinediones/analysis , Thiazolidinediones/chemistry , Urea/analogs & derivativesABSTRACT
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.
Subject(s)
Receptor, Cholecystokinin A/antagonists & inhibitors , Receptor, Cholecystokinin B/antagonists & inhibitors , Molecular Structure , StereoisomerismABSTRACT
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.
