155339-52-9Relevant academic research and scientific papers
Synthesis of 1,5,6,7-tetrahydro-4H-pyrazolo[4,3-c]pyridin-4-ones as conformationally constrained pyrazole analogues of histamine
Zerovnik, Darja,Groselj, Uros,Kralj, David,Malavasic, Crt,Bezensek, Jure,Dahmann, Georg,Stare, Katarina,Meden, Anton,Stanovnik, Branko,Svete, Jurij
experimental part, p. 3363 - 3373 (2010/11/19)
Three synthetic methods for the preparation of 1,5-disubstituted 1,5,6,7-tetrahydro-4H-pyrazolo[4,3-c]pyridin-4-ones as heterocyclic histamine analogues were developed. The first method starts from easily available methyl 5-(2-aminoethyl)-1H-pyrazole-4-carboxylates, which were N-alkylated and the resulting secondary amines were cyclised in the presence of a base to give the title compounds in 17-92% yields (method A). Alternatively, the amines were first cyclised to the 5-unsubstituted pyrazolo[4,3-c]pyridin-4-ones. Subsequent N-benzylation afforded three of the title compounds in 36-49% yields (method B). The third method comprises a six-step transformation of methyl acrylate into 1-benzylpiperidine-2,4-dione. Treatment of the latter with N,N-dimethylformamide dimethylacetal (DMFDMA) followed by acid-catalysed cyclisation of the formed enaminone with methyl-, phenyl- and tert-butylhydrazine afforded the same three title compounds in 79-87% yields (method C). Georg Thieme Verlag Stuttgart New York.
Synthesis of 6- and 7-membered cyclic enaminones: Scope and mechanism
Niphakis, Micah J.,Turunen, Brandon J.,Georg, Gunda I.
supporting information; experimental part, p. 6793 - 6805 (2010/12/20)
Six- and seven-membered cyclic enaminones can be prepared using common, environmentally benign reagents. Amino acids are used as synthetic precursors allowing diversification and the incorporation of chirality. The key reaction in this multistep process involves deprotection of Boc-amino ynones and subsequent treatment with methanolic K2CO3 to induce cyclization. A β-amino elimination side reaction was identified in a few labile substrates that led to either loss of stereochemical purity or degradation. This process can be mitigated in specific cases using mild deprotection conditions. NMR and deuterium-labeling experiments provided valuable insight into the workings and limitations of this reaction. Although disguised as a 6-endo-dig cyclization, the reagents employed in the transformation play a direct role in bond-making and bond-breaking, thus changing the mode of addition to a 6-endo-trig cyclization. This method can be used to construct an array of monocyclic and bicyclic scaffolds, many of which are found in well-known natural products (e.g., indolizidine, quinolizidine, and Stemona alkaloids).
Synthesis of β-amino arylketones through the addition of ArLi derivatives to β-aminoesters
Lima, Paulo G.,Sequeira, Lucia C.,Costa, Paulo R.R.
, p. 3525 - 3527 (2007/10/03)
2-Lithiumthiophene and 2-lithiumpyridine were allowed to react with N-substituted β-aminoesters. Only β-amino arylketones were obtained from N-BOC, N-H derivatives, while arylenoates were formed (retro-conjugate addition) from those substrates bearing N-Bn, N-H substituents, despite the aryllithium used. When the nitrogen is disubstituted (BOC and Bn), the product distribution depended on the nucleophile, leading to tertiary alcohols for 2-lithiumthiophene or ketones for 2-lithiumpyridine. Tertiary alcohols were also formed when PhLi was used as a nucleophile.
Tandem Michael reactions for the construction of pyrrolidine and piperidine ring systems
Barco,Benetti,Casolari,Pollini,Spalluto
, p. 3039 - 3042 (2007/10/02)
A convergent one-pot construction of disubstituted pyrrolidine and piperidine frameworks has been accomplished through a simple protocol involving intermolecular conjugate addition of a nitrogen nucleophile to an electrophilic olefin followed by intramolecular trapping of the generated enolate by a built-in α,β-unsaturated acceptor.
