Convergent, Kilogram Scale Synthesis of an Akt Kinase Inhibitor
| العنوان: | Convergent, Kilogram Scale Synthesis of an Akt Kinase Inhibitor |
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| المؤلفون: | R. Scott Hoerrner, Juan D. Arredondo, C. Scott Shultz, Takahiro Itoh, Xianghui Wen, Debra J. Wallace, Jason L. Nyrop, Dalian Zhao, Paul G. Bulger, Daniel J. Muzzio, Lushi Tan, Ephraim M. Bassan, Qinghao Chen, Mark Weisel, Sarah J. Dolman, Chengfu Xie, Pintipa Grongsaard |
| المصدر: | Organic Process Research & Development. 16:1069-1081 |
| بيانات النشر: | American Chemical Society (ACS), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | chemistry.chemical_compound, Temperature and pressure, Deprotonation, Chemistry, Stereochemistry, Organic Chemistry, Hydrazine, Allosteric regulation, Diastereomer, Molecule, Physical and Theoretical Chemistry, Formylation, Cyclobutane |
| الوصف: | The development of a convergent, chromatography-free synthesis of an allosteric Akt kinase inhibitor is described. The route comprised 17 total steps and was used to produce kilogram quantities of the target molecule. A key early transformation, for which both batch and flow protocols were developed, was formylation of a dianion derived by deprotonation and subsequent lithium-halogen exchange from a 2-bromo-3-aminopyridine precursor. Improved reaction yield and practicality were achieved in the continuous processing mode. Further significant process developments included the safe execution of a high temperature and pressure hydrazine displacement, separation of substituted cyclobutane diastereomers by means of chemoselective ester hydrolysis, and a late-stage Suzuki fragment coupling under mild conditions. |
| تدمد: | 1520-586X 1083-6160 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::317d3d594c7cd2a3aab48392e1bc47ab https://doi.org/10.1021/op300031r |
| رقم الأكسشن: | edsair.doi...........317d3d594c7cd2a3aab48392e1bc47ab |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 1520586X 10836160 |
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