1073117-57-3Relevant academic research and scientific papers
Synthesis of Methyl 7,9-Dimethyl-5-oxo-2,3,4,5-tetrahydro-1 H -benzo[ b ]azepine-1-carboxylate and Its Analogues
Vaid, Radhe K.,Boini, Sathish K.,Alt, Charles A.,Spitler, Jeremy T.,Hadden, Chad E.,Frank, Scott A.,Moher, Eric D.
, p. 2463 - 2470 (2014)
A high-yielding five-step synthesis of the title compound, methyl 7,9-dimethyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate, starting from 2,4-dimethylaniline was developed. This synthesis involved N-alkylation of 2,4-dimethylaniline with ethyl 4-bromobutyrate to obtain ethyl 4-[(2,4-dimethylphenyl)amino]butanoate. Carbamoylation of the latter followed by hydrolysis of the resulting ester provided 4-[(2,4-dimethylphenyl) (methoxycarbonyl)amino]butanoic acid. Activation of the carboxylic acid using thionyl chloride followed by intramolecular cyclization via a Friedel-Crafts reaction using aluminum trichloride provided the title compound in good yield. Analogues of the title compound were also prepared similarly. Georg Thieme Verlag Stuttgart New York.
Synthesis of Methyl 7,9-Dimethyl-5-oxo-2,3,4,5-tetrahydro-1 H -benzo[ b ]azepine-1-carboxylate and Its Analogues
Vaid, Radhe K.,Boini, Sathish K.,Alt, Charles A.,Spitler, Jeremy T.,Hadden, Chad E.,Frank, Scott A.,Moher, Eric D.
, p. 2463 - 2470 (2015/12/26)
A high-yielding five-step synthesis of the title compound, methyl 7,9-dimethyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate, starting from 2,4-dimethylaniline was developed. This synthesis involved N-alkylation of 2,4-dimethyl aniline with ethyl 4-bromobutyrate to obtain ethyl 4-[(2,4-dimethylphenyl)amino]butanoate. Carbamoylation of the latter followed by hydrolysis of the resulting ester provided 4-[(2,4-dimethylphenyl)(methoxycarbonyl)amino]butanoic acid. Activation of the carboxylic acid using thionyl chloride followed by intramolecular cyclization via a Friedel-Crafts reaction using aluminum trichloride provided the title compound in good yield. Analogues of the title compound were also prepared similarly.
Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121)
Bonfanti, Jean-Fran?ois,Meyer, Christophe,Doublet, Frédéric,Fortin, Jér?me,Müller, Philippe,Queguiner, Laurence,Gevers, Tom,Janssens, Peggy,Szel, Heidi,Willebrords, Rudy,Timmerman, Philip,Wuyts, Koen,Van Remoortere, Pieter,Janssens, Frans,Wigerinck, Piet,Andries, Koen
, p. 875 - 896 (2008/09/19)
A preceding paper (Bonfanti et al. J. Med Chem. 2007, 50, 4572-4584) reported the optimization of the pharmacokinetic profile of substituted benzimidazoles by reducing their tissue retention. However, the modifications that were necessary to achieve this goal also led to a significant drop in anti-RSV activity. This paper describes a molecular modeling study followed by a lead optimization program that led to the recovery of the initial potent antiviral activity and the selection of TMC353121 as a clinical candidate.
