TY - JOUR AU - Roy, Deblina; Panda, Gautam TI - Base-Mediated 1,6-Aza-Michael Addition of Heterocyclic Amines and Amides to para-Quinone Methides Leading to Meclizine-, Hydroxyzine- and Cetirizine-like Architectures SN - 0039-7881 SN - 1437-210X PY - 2019 JO - Synthesis JF - Synthesis LA - EN VL - 51 IS - 23 SP - 4434 EP - 4442 ET - 2019/09/13 DA - 2019/11/14 KW - trisubstituted methanes KW - aza-Michael addition KW - para-quinone methides KW - zine-like architectures KW - heterocyclic amines and amides AB - An expeditious, cost-effective synthetic methodology for a wide range of nitrogen-containing unsymmetrical trisubstituted methanes (TRSMs) is reported. The synthesis involves base-mediated 1,6-conjugate addition of heterocyclic amines and amides to substituted para-quinone methides, giving the unsymmetrical TRSMs in moderate to very good yields (up to 83%) in one pot. The low cost, mild temperature, high atom economy and yields, easy scale-up and broad substrate scope are some of the salient features of this protocol. Further, the methodology could be extended for the synthesis of meclizine-, ­hydroxyzine- and cetirizine-like molecules. The structure of one such compound, 2,6-di-tert-butyl-4-((4-chlorophenyl)(4-methylpiperazin-1-yl)methyl)phenol, was determined by single crystal X-ray analysis. PB - © Georg Thieme Verlag DO - 10.1055/s-0039-1690677 UR - http://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0039-1690677 ER -