C:Corrosive;17740-40-8Relevant articles and documents
Streamlined Synthesis of a Bicyclic Amine Moiety Using an Enzymatic Amidation and Identification of a Novel Solid Form
Brown, Maria S.,Caporello, Michaella A.,Goetz, Adam E.,Johnson, Amber M.,Jones, Kris N.,Knopf, Kevin M.,Kulkarni, Samir A.,Lee, Taegyo,Li, Bryan,Lu, Cuong V.,Magano, Javier,Puchlopek-Dermenci, Angela L. A.,Reyes, Giselle P.,Ruggeri, Sally Gut,Wei, Lulin,Weisenburger, Gerald A.,Wisdom, Richard A.,Zhang, Mengtan
, p. 1419 - 1430 (2021)
We describe a series of improvements to the synthesis of a 3,8-diazabicyclo[3.2.1]octane derivative that result in a reduced step count and higher overall efficiency compared to previously published syntheses. Our method includes optimization and mechanistic understanding of a key diastereoselective cyclization to achieve a >95:5 diastereomeric ratio, as well as demonstration of a unique enzyme-catalyzed amidation reaction using hexamethyldisilazane as both an ammonia source and scavenger. Finally, we identify a novel cocrystal solid form of the target compound that provides improved purity and material properties. Demonstration of the new chemistry to prepare >100 kg of the target compound serves to illustrate the robustness of the new process.
Synthesis of bridged bicyclic amino alcohols as compact modules for medicinal chemistry
Wu, Guolong,Wang, Di,Zhu, Wei,Shen, Hong,Liu, Haixia,Fu, Lei
supporting information, p. 12 - 21 (2019/01/04)
The efficient synthetic routes of three bridged bicyclic amino alcohols were reported. It is conceivable that these compounds could be readily used as compact modules in medicinal chemistry to fine-tune physicochemical and pharmacokinetic properties, in order to eventually improve the overall quality of small molecule drug candidates.
N-benzenesulfonyl L-proline compounds as bradykinin antagonists
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Page 12, (2010/01/31)
This invention provides a compound of the formula (I): or the pharmaceutically acceptable salts thereof wherein X1 and X2 are halo; R1 andR2 are independently hydrogen or C1-4 alkyl; R3 and R4 are each hydrogen or halo; andR5 is(a) -C3-9 diazacycloalkyl optionally substituted with C5-11 azabicycloalkyl;(b) -C3-9 azacycloalkyl-NH-(C5-11 azabicycloalkyl optionally substituted with C1-4 alkyl);(c) -NH-C1-3 alkyl-C(O)-C5-11 diazabicycloalkyl;(d) -NH-C1-3 alkyl-C(O)-NH-C5-11 azabicycloalkyl, the C5-11 azabicycloalkyl being optionally substituted with C1-4 alkyl;(e) -C3-9 azacycloalkyl optionally substituted with C3-9 azacycloalkyl; or(f) -NH-C1-5 alkyl-NH-C(O)-C4-9 cycloalkyl-NH2. These compounds are useful for the treatment of medical conditions mediated by bradykinin such as inflammation, allergic rhinitis, pain, etc. This invention also provides a pharmaceutical composition comprising the above compound.
