Facile scalable reduction of N-acylated dihydropyrazoles.
The reduction of a variety of highly functionalized N-acylated dihydropyrazoles (1) with BH3 x pyridine is described. The process through which this unexpectedly difficult reduction was discovered and developed is reported. A facile atom-efficient route to the N-acylated dihydropyrazole reduction precursors (1) is also illustrated. The resulting acylpyrazolidine products (2) that arise upon reduction were isolated in good to high yields following exposure to reaction conditions which have been shown to tolerate a variety of different functional groups. Finally, this route has been demonstrated on a kilogram scale and provides direct access to potential proline surrogates for peptidomimetic applications.
Curtis
Michael D
MD
Chemical Development, Procter & Gamble Pharmaceuticals, P.O. Box 191, Norwich, New York 13815, USA. curtis.md@pg.com
Hayes
Nancy C
NC
Matson
Patricia A
PA
D000215:Acylation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D011720:Pyrazoles