1392314-60-1Relevant articles and documents
Amine over-alkylation side products in the synthesis of BMS-955176
Ayers, Sloan,Xu, Zhongmin,Haley, Matthew,Yang, Alice,Black, Regina,Kiau, Susanne
, p. 2664 - 2667 (2018)
Over-alkylation side products are common in the alkylation of amines by substitution. In the synthesis of the novel HIV Maturation inhibitor BMS-955176, two over-alkylation byproducts were routinely observed at the penultimate synthetic step, in which a thiomorpholine dioxide side chain was added to the core molecule by alkylation of a primary amine. These two byproducts had drastically different HPLC relative retention times, despite both containing only one additional side chain. Adding complexity to the challenge of solving their structures was the proclivity of the two byproducts to interconvert. Positive- and negative-ion HRMS, as well as isolation and 1D and 2D NMR were utilized to determine their structures. These byproducts were additionally problematic in that they led to daughter impurities at the API step.
Synthesis of HIV-Maturation Inhibitor BMS-955176 from Betulin by an Enabling Oxidation Strategy
Ortiz, Adrian,Soumeillant, Maxime,Savage, Scott A.,Strotman, Neil A.,Haley, Matthew,Benkovics, Tamas,Nye, Jeffrey,Xu, Zhongmin,Tan, Yichen,Ayers, Sloan,Gao, Qi,Kiau, Susanne
, p. 4958 - 4963 (2017/05/12)
A concise and scalable second generation synthesis of HIV maturation inhibitor BMS-955176 is described. The synthesis is framed by an oxidation strategy highlighted by a CuI mediated aerobic oxidation of betulin, a highly selective PIFA mediated dehydrogenation of an oxime, and a subsequent Lossen rearrangement which occurs through a unique reaction mechanism for the installation of the C17 amino functionality. The synthetic route proceeds in 7 steps with 47% overall yield and begins from the abundant and inexpensive natural product betulin.
C-19 MODIFIED TRITERPENOIDS WITH HIV MATURATION INHIBITORY ACTIVITY
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Page/Page column, (2014/08/19)
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, C-19 modified triterpenoids that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I and II: These compounds are useful for the treatment of HIV and AIDS.
