505083-10-3Relevant articles and documents
Development of a practical synthesis of an aminoindanol-derived m1 agonist
Hansen, Marvin M.,Borders, Sandra S.K.,Clayton, Marcella T.,Heath, Perry C.,Kolis, Stanley P.,Larsen, Samuel D.,Linder, Ryan J.,Reutzel-Edens, Susan M.,Smith, Justin C.,Tameze, Sheila L.,Ward, Jeffrey A.,Weigel, Leland O.
experimental part, p. 198 - 208 (2010/04/22)
An efficient and scalable synthesis of the clinical candidate 1 is described. The first-generation synthesis built the enantioenriched nitro-aminoindanol core from 6-nitroindanone using a five-step literature route. The second-generation route used a safe aromatic nitration protocol in the presence of the unprotected alcohol to afford the requisite nitro-aminoindanol in one step. Challenges addressed in the remainder of the synthesis include a nitro group reduction to afford ppm levels of unreacted Ar-NO2 (a mutagen) and a novel amidine formation under mild conditions via DMAP/K2CO3-promoted reaction with a thioimidate-activated amide. A convenient protocol for freebasing the API was provided by stirring with solid K2CO3 and monitoring disappearance of HI by reverse-phase HPLC.
