| 摘要 |
Synthetic pathways are disclosed for synthesizing derivatives or analogs of fentanyl. Specifically set out are pathways for synthesizing alfentanil, sufentanil and remifentanil. The disclosed methods require fewer steps and produce a greater yield of product than methods reported in the prior art. The pathways to all these compounds begin with a common pathway of condensing a piperidone with a primary amine so as to form a 4-amino carboxyamino-piperidine, wherein N of said piperidone is a -N-COO-(CH<SUB>2</SUB>)<SUB>n</SUB>CH<SUB>3</SUB>, alkylating an N of said primary amine which was condensed with said piperidone thereby producing an N-alkyl-anilide, and hydrolyzing said -COO-(CH<img id="CUSTOM-CHARACTER-00001" he="2.79mm" wi="1.44mm" file="US07074935-20060711-P00001.TIF" alt="custom character" img-content="character" img-format="tif"/><SUP>2</SUP>)<SUB>n</SUB><SUP>CH</SUP>3? group of said 4-amino-4-carboxyamino-piperidine following the condensation reaction so as to form a piperidine hydrolysis product. This product can then be convened to remifentanil in a 4 step reaction. Also, this hydrolysis product can be treated with a hydride to yield a 4-hydroxymthyl-piperidine which can be converted to alfentanil in 3 further steps, to sufentanil in 3 more steps, or to a variety of remifentanil analogs in two steps. |
