Patent ID: 8354536
Filing Date: 2013-01-15
Classification: A61P,C07D

Abstract:
1. A method for preparing compound (1) having the formula: wherein R 1 is wherein R R and m is 1, 2 or 3; or R 1 is A 1 , wherein A 1 is wherein R H, C C C cycloalkyl having 3 to 10, preferably 3 to 8 carbon atoms, which is unsubstituted or substituted one or more times by halogen, hydroxy, oxo, cyano, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, or combinations thereof (e.g., cyclopentyl), cycloalkylalkyl having 4 to 16, preferably 4 to 12 carbon atoms, which is unsubstituted or substituted in the cycloalkyl portion and/or the alkyl portion one or more times by halogen, oxo, cyano, hydroxy, C Ar-alkyl (e.g., benzyl), or Het-alkyl (e.g., thienylmethyl); wherein Ar Ar-alkyl Het R R m is as described above; and o is 1 or 2; or R 1 is comprising reacting compound (3) with a bicycloamine of formula R 1 —H in the presence of a peptide coupling reagent, the improvement comprising (a) reacting 5-trifluoromethoxyisatin with a ketone-protecting reagent in a solvent to provide a ketone-protected compound; (b) treating the ketone-protected compound from step (a) with an electrophilic aminating reagent in an inert solvent to provide an electrophilically aminated compound; and (c) hydrolyzing the electrophilically aminated compound from step (b) under basic conditions to form a ring opened intermediate and treating the intermediate with aqueous acid to ring close the intermediate and remove the ketone-protecting reagent to provide (3).