title: Stereoselective synthesis of spiropiperidines as BACE-1 aspartyl protease inhibitors via late stage N-arylation of a 1,8-diazaspiro[4.5]dec-3-en-2-one pharmacophore.
abstract: A stereoselective synthesis of spiropiperidine compounds, exemplified by compound 1, was developed, which was based upon the late stage N-arylation of a 1,8-diazaspiro[4.5]dec-3-en-2-one pharmacophore. Previously, compound 1 was prepared in low overall yield from piperidinone 2 via the Strecker reaction. A new route was developed, which employed the stereospecific Corey-Link reaction of an enantiomerically pure trichloromethylcarbinol to give a template compound amenable to late stage N-arylation.
authors: Pfizer Worldwide Research and Development, Neuroscience Medicinal Chemistry, Eastern Point Road, Groton, Connecticut 06340, United States. chewah.lee@pfizer.com
authors: Che-Wah
authors: CW
authors: Lee
authors: Ricardo
authors: R
authors: Lira
authors: Jason
authors: J
authors: Dutra
authors: Kevin
authors: K
authors: Ogilvie
authors: Brian T
authors: BT
authors: O'Neill
authors: Michael
authors: M
authors: Brodney
authors: Christopher
authors: C
authors: Helal
authors: Joseph
authors: J
authors: Young
authors: Erik
authors: E
authors: Lachapelle
authors: Subas
authors: S
authors: Sakya
authors: John C
authors: JC
authors: Murray
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011480:Protease Inhibitors; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C584066:(5R,7S)-1-(3-fluorophenyl)-8-(3-isopropoxybenzyl)-7-methyl-1,8-diazaspiro(4.5)dec-3-en-2-one; D001372:Aza Compounds; D010880:Piperidines; D011480:Protease Inhibitors; D013141:Spiro Compounds; D016282:Aspartic Acid Endopeptidases; D000432:Methanol