56464-70-1Relevant articles and documents
Facile Access to 1,4-Disubstituted Pyrrolo[1,2- a ]pyrazines from α-Aminoacetonitriles
Basha, Mushkin,Belema, Makonen,Dhar, T. G. Murali,Gupta, Anuradha,Gupta, Arun Kumar,Indasi, Gopi Kumar,Karmakar, Ananta,Mathur, Arvind,Meanwell, Nicholas A.,Ramalingam, Sridharan,Rampulla, Richard
supporting information, p. 441 - 449 (2020/01/23)
An efficient and practical synthetic protocol for the synthesis of 1,4-disubstituted pyrrolo[1,2- a ]pyrazine derivatives is described that originates from α-substituted pyrroloacetonitriles which, in turn, are readily available from aryl and alkyl aldehydes. The α-pyrroloacetonitriles were subjected to a Friedel-Crafts acylation with methyl chlorooxoacetate followed by reduction of the nitrile group under Pd-catalyzed hydrogenation conditions and finally aromatization with DDQ leading to the desired pyrrolo[1,2- a ]pyrazine derivatives. This method was generalized and successfully applied to various aryl, heteroaryl, and alkyl substrates. The developed protocol provides direct and convenient access to 1,4-disubstituted ring systems in moderate to good overall yields (51-68percent) without the need for purification of the intermediates. Further functionalization via the stepwise halogenation (bromination, iodination) and nitration was also demonstrated. In addition, the potential of the ester functionality for elaboration was demonstrated by manipulating into heterocyclic ring systems, exemplified by conversion into benzoxazole derivatives.
A Sustainable, Semi-Continuous Flow Synthesis of Hydantoins
Vukeli?, Stella,Koksch, Beate,Seeberger, Peter H.,Gilmore, Kerry
supporting information, p. 13451 - 13454 (2016/09/13)
Hydantoins are an important class of heterocycles with applications in pharmacy, agriculture, and as intermediates in organic synthesis. Traditional synthetic procedures to access hydantoins are target oriented with multiple synthetic steps and often use reagents that are not commercially available or sustainable. Herein, an efficient process is described for accessing hydantoins starting from commercially available amines using consecutive gas–liquid transformations (oxygen, carbon dioxide). This semi-continuous process produced ten benzylic/aliphatic hydantoins in good overall yields (52–84 %).
Flow synthesis of fluorinated α-amino acids
Vukelic, Stella,Ushakov, Dmitry B.,Gilmore, Kerry,Koksch, Beate,Seeberger, Peter H.
supporting information, p. 3036 - 3039 (2015/05/13)
Fluorinated α-amino acids are versatile compounds that are used for many purposes in medicinal and biochemistry. However, their synthesis remains a significant hurdle, often requiring multiple steps, multiple protecting groups, and/or the use of highly toxic reagents. These challenges have limited the application of fluorinated α-amino acids. A convenient, protecting-group-free and semi-continuous process for the synthesis of racemic fluorinated α-amino acids from fluorinated amines is described. Following a singlet-oxygen-driven photooxidative cyanation, an acid-mediated hydrolysis of the intermediate α-amino nitrile yields the desired α-amino acid. Aliphatic, benzylic, and homobenzylic residues with different fluorination degrees are tolerated, providing good overall yields (50-67?%). This semi-continuous process is particularly advantageous for an aliphatic amine, the intermediate α-amino nitrile of which decomposes upon isolation. An efficient, semi-continuous, and protecting-group-free method for the synthesis of fluorinated α-amino acids from the corresponding amines has been developed. A low temperature photooxidative cyanation of benzylic and aliphatic amines provided α-amino nitriles with varying fluorination patterns. These unstable intermediates were trapped with an acid-mediated hydrolysis with good overall yields.
