A new approach towards 1-phenyl and 1-benzyl substituted 2-(aminomethyl)cyclopropanecarboxamides as novel derivatives of the antidepressant Milnacipran.
2-(2-Cyano-2-phenylethyl)aziridines were converted into novel trans-2-aminomethyl-1-phenylcyclopropanecarboxamides via regiospecific ring opening and 3-exo-tet cyclisation, thus providing the first convenient entry into the trans-isomer of Milnacipran as a useful template for further derivatisation. Furthermore, unprecedented 2-aminomethyl-1-benzylcyclopropanecarboxamides have been synthesized using two different routes starting from 2-(2-cyanoethyl)aziridines, both involving alpha-benzylation with respect to the nitrile group and aziridine to cyclopropane ring transformation.
Vervisch
Karel
K
Dep. of Organic Chemistry, Fac. of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium.
D'hooghe
Matthias
M
Törnroos
Karl W
KW
De Kimpe
Norbert
N
D000928:Antidepressive Agents / Q000138:chemical synthesis*; D001388:Aziridines / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry*; D000078764:Milnacipran; D008958:Models, Molecular; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry
D000928:Antidepressive Agents; D001388:Aziridines; D003521:Cyclopropanes; D009570:Nitriles; D000078764:Milnacipran