Facile reductive amination of aldehydes with electron-deficient anilines by acyloxyborohydrides in TFA: application to a diazaindoline scale-up.
A scale-up of diazaindoline 1 was achieved in four stages and 32% overall yield. The key step involved rapid reductive amination of aldehyde 8 with aniline 5 by sodium triacetoxyborohydride (STAB-H) and TFA followed by ring closure of intermediate amine 9 to compound 1 in the same pot. These reaction conditions were also applied to facile reductive aminations with anilines known to have little reactivity under STAB-H/AcOH conditions. Spectral data supported the tris(trifluoroacetoxy)borohydride anion (16) as the active reducing agent.
Boros
Eric E
EE
GlaxoSmithKline Research & Development, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA. eric.e.boros@gsk.com
Thompson
James B
JB
Katamreddy
Subba R
SR
Carpenter
Andrew J
AJ
D000447:Aldehydes / Q000737:chemistry*; D000586:Amination; D000814:Aniline Compounds / Q000737:chemistry*; D001372:Aza Compounds / Q000737:chemistry*; D001880:Boranes / Q000737:chemistry*; D004583:Electrons; D005449:Fluorenes / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D010084:Oxidation-Reduction
D000447:Aldehydes; D000814:Aniline Compounds; D001372:Aza Compounds; D001880:Boranes; D005449:Fluorenes; D007211:Indoles; C512801:trifluorenylamine; C023650:aniline