Reaction for the synthesis of benzimidazol-2-ones, imidazo[5,4-b]-, and imidazo[4,5-c]pyridin-2-ones via the rearrangement of quinoxalin-2-ones and their aza analogues when exposed to enamines.

A synthetically useful protocol has been developed for the preparation of highly functionalized N-pyrrolylbenzimidazol-2-ones. The reaction of variously substituted 3-aroyl- and 3-alkanoylquinoxalin-2(1H)-ones with commercially available enamines in acetic acid results in a rapid rearrangement and formation of N-pyrrolylbenzimidazol-2-ones in modest to excellent yields. The key step of the rearrangement involves the novel ring contraction of 3-aroyl- and 3-alkanoylquinoxalin-2(1H)-ones with enamines. In this case, the atom of carbon which is displaced from the pyrazine ring of quinoxalin-2(1H)-one becomes the fourth carbon atom of the newly formed pyrrole ring. The method is applicable for the aza analogues of quinoxalin-2(1H)-ones.

[1]  N. Zhukova,et al.  An efficient metal-free synthesis of 2-(pyrazin-2-yl)benzimidazoles from quinoxalinones and diaminomaleonitrile via a novel rearrangement , 2012 .

[2]  V. Mamedov,et al.  Recyclization reactions leading to benzimidazoles , 2011 .

[3]  S. Boncel,et al.  Michael versus retro-Michael reaction in the regioselective synthesis of N-1 and N-3 uracil adducts , 2010 .

[4]  E. De Clercq,et al.  Novel 1,3-dihydro-benzimidazol-2-ones and their analogues as potent non-nucleoside HIV-1 reverse transcriptase inhibitors. , 2010, Bioorganic & medicinal chemistry.

[5]  V. Singh,et al.  Asymmetric organocatalytic Michael-type reaction of phosphorus ylides to nitroolefins: synthesis of γ-nitro-β-aryl-α-methylene carboxylic esters , 2010 .

[6]  Yongwen Jiang,et al.  Assembly of substituted 1H-benzimidazoles and 1,3-dihydrobenzimidazol-2-ones via CuI/L-proline catalyzed coupling of aqueous ammonia with 2-iodoacetanilides and 2-iodophenylcarbamates. , 2009, The Journal of organic chemistry.

[7]  A. Gubaidullin,et al.  Efficient synthesis of 2-(pyrazol-3-yl)benzimidazoles from 3-arylacylidene-3,4-dihydroquinoxalin-2(1H)-ones and hydrazine hydrate via a novel rearrangement , 2009 .

[8]  C. Pannecouque,et al.  Design, synthesis, and structure-activity relationships of 1,3-dihydrobenzimidazol-2-one analogues as anti-HIV agents. , 2009, Bioorganic & medicinal chemistry.

[9]  A. Gubaidullin,et al.  An efficient one-step method for the synthesis of 2-(indolizin-2-yl)benzimidazoles from quinoxalinones and α-picoline via a novel rearrangement , 2008 .

[10]  R. SanMartin,et al.  Copper-catalyzed intramolecular N-arylation of ureas in water: a novel entry to benzoimidazolones , 2008 .

[11]  Hualiang Jiang,et al.  Copper-catalyzed intramolecular cyclization to N-substituted 1,3-dihydrobenzimidazol-2-ones. , 2008, Organic letters.

[12]  V. Mamedov,et al.  Quinoxaline-benzimidazole rearrangements in the reactions of 3-alkanoylquinoxalin-2-ones with 1,2-phenylenediamines , 2007 .

[13]  D. Ma,et al.  Cascade coupling/cyclization process to N-substituted 1,3-dihydrobenzimidazol-2-ones. , 2007, Organic letters.

[14]  A. Marino,et al.  Respiratory syncytial virus fusion inhibitors. Part 4: optimization for oral bioavailability. , 2007, Bioorganic & medicinal chemistry letters.

[15]  Y. Zong,et al.  Microwave-assisted traceless synthesis of benzimidazolones , 2007 .

[16]  M. Hao,et al.  Discovery and design of benzimidazolone based inhibitors of p38 MAP kinase. , 2006, Bioorganic & medicinal chemistry letters.

[17]  Cory R. Theberge,et al.  Identification of novel, orally bioavailable spirohydantoin CGRP receptor antagonists. , 2006, Bioorganic & medicinal chemistry letters.

[18]  M. Guillaume.  Expeditious process improvement for the synthesis of RWJ-333966 , 2006 .

[19]  I. Davies,et al.  Efficient access to cyclic ureas via Pd-catalyzed cyclization. , 2006, Organic letters.

[20]  R. Winneker,et al.  SAR studies of 6-aryl-1,3-dihydrobenzimidazol-2-ones as progesterone receptor antagonists. , 2005, Bioorganic & medicinal chemistry letters.

[21]  Jan Balzarini,et al.  Computational strategies in discovering novel non-nucleoside inhibitors of HIV-1 RT. , 2005, Journal of medicinal chemistry.

[22]  Jianmei Wei,et al.  Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors. , 2005, Bioorganic & medicinal chemistry letters.

[23]  M. Kassiou,et al.  Synthesis, radiosynthesis and in vivo evaluation of 5-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]-1,3-dihydrobenzoimidazol-2-[(11)C]one, as a potent NR(1A)/2B subtype selective NMDA PET radiotracer. , 2003, Bioorganic & medicinal chemistry.

[24]  C. Claver,et al.  Synthesis of 2-substituted-benzothiazoles by palladium-catalyzed intramolecular cyclization of o-bromophenylthioureas and o-bromophenylthioamides , 2003 .

[25]  A. Alexakis,et al.  Asymmetric Michael Addition of α-Hydroxyketones to Nitroolefins Catalyzed by Chiral Diamine , 2003 .

[26]  S. Matsunaga,et al.  Direct catalytic asymmetric Michael reaction of hydroxyketones: asymmetric Zn catalysis with a Et2Zn/linked-BINOL complex. , 2003, Journal of the American Chemical Society.

[27]  D Horvath,et al.  From hit to lead. Combining two complementary methods for focused library design. Application to mu opiate ligands. , 2001, Journal of medicinal chemistry.

[28]  Y. Iwasawa,et al.  Synthesis of J-113397, the first potent and selective ORL1 antagonist , 2001 .

[29]  A. Orjales,et al.  2,3-Dihydro-2-oxo-1H-benzimidazole-1-carboxamides with selective affinity for the 5-HT(4) receptor: synthesis and structure-affinity and structure-activity relationships of a new series of partial agonist and antagonist derivatives. , 1999, Journal of medicinal chemistry.

[30]  W. Vaalburg,et al.  Synthesis and evaluation of (S)-4-(3-(2'-[C-11]isopropylamino)-2-hydroxy-propoxy)-2H-benzimidazol-2-one ((S)-[C-11]CGP 12388) and (S)-4-(3-((1'-[F-18]-fluoroisopropyl)amino)-2-hydroxypropoxy)-2H-benzimidazol-2-one ((S)-[F-18]Fluoro-CGP 12388) for visualization of beta-adrenoceptors with positron emi , 1997 .

[31]  A. J. Shaka,et al.  One-Dimensional NOE Experiments Using Pulsed Field Gradients , 1997 .

[32]  A. J. Shaka,et al.  Excitation Sculpting in High-Resolution Nuclear Magnetic Resonance Spectroscopy: Application to Selective NOE Experiments , 1995 .

[33]  Z. Rappoport.  The chemistry of enamines , 1994 .

[34]  R. Henning,et al.  Synthesis and neuroleptic activity of a series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzim idazolone derivatives. , 1987, Journal of medicinal chemistry.