Annulation of primary amines to piperazines and diazaspirocycles utilizing alpha-methyl benzyl resin.
The microwave-assisted solid-phase synthesis of piperazines, 3,9-diazaspiro[5.5]undecanes and 2,9-diazaspiro[5.5]undecanes is reported. The synthesis relies on the direct annulation of primary amines with resin-bound bismesylates. Critical to the success of this chemistry was the development of alpha-methyl benzyl carbamate resin linker. This resin permits the cleavage of the heterocycles under mildly acidic conditions, free of contaminating linker-derived N-alkylated byproducts.
Macleod
Calum
C
Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, Pennsylvania 19341, USA.
Martinez-Teipel
Blanca I
BI
Barker
William M
WM
Dolle
Roland E
RE
D000588:Amines / Q000737:chemistry*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008698:Mesylates / Q000737:chemistry; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D000588:Amines; D001372:Aza Compounds; D002219:Carbamates; D008698:Mesylates; D010879:Piperazines; D012117:Resins, Synthetic; D013141:Spiro Compounds