| Autor: |
Smith AC; Pfizer Worldwide Research & Development , Eastern Point Road, Groton, Connecticut 06340, United States., Cabral S; Pfizer Worldwide Research & Development , Eastern Point Road, Groton, Connecticut 06340, United States., Kung DW; Pfizer Worldwide Research & Development , Eastern Point Road, Groton, Connecticut 06340, United States., Rose CR; Pfizer Worldwide Research & Development , Eastern Point Road, Groton, Connecticut 06340, United States., Southers JA; Pfizer Worldwide Research & Development , Eastern Point Road, Groton, Connecticut 06340, United States., García-Irizarry CN; Pfizer Worldwide Research & Development , Eastern Point Road, Groton, Connecticut 06340, United States., Damon DB; Pfizer Worldwide Research & Development , Eastern Point Road, Groton, Connecticut 06340, United States., Bagley SW; Pfizer Worldwide Research & Development , Eastern Point Road, Groton, Connecticut 06340, United States., Griffith DA; Pfizer Worldwide Research & Development , Eastern Point Road, Groton, Connecticut 06340, United States. |
| Abstrakt: |
The synthesis of a series of pharmaceutically important N-protected methyl-substituted spirocyclic piperidine-azetidine (2,7-diazaspiro[3.5]nonane) and spirocyclic piperidine-pyrrolidine (2,8-diazaspiro[4.5]decane) ring systems was developed. These motifs contain two differentiated sites (protected secondary amines) to allow for further functionalization via reductive amination, amidation, or other chemistry. The methyl-substituted spiroazetidine ring systems were accessed using nitrile lithiation/alkylation chemistry while the methyl-substituted spiropyrrolidines were synthesized by 1,4-addition reactions with nitroalkanes, followed by reduction and cyclization. These conditions were then scaled for the synthesis of 1-methyl spirocyclic piperidine-pyrrolidine with a classical resolution of the product using a tartaric acid derivative to isolate a single enantiomer. |
