Process for trans-6- 2-(substituted-pyrrol-1-yl)alkyl!pyran-2-one inhibitors of cholesterol synthesis
AssigneeWarner-Lambert Company
InventorsDonald E. Butler, Tung Van Le, Thomas N. Nanninga
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Abstract
An improved process for the preparation of trans-6- 2-(substituted-pyrrole-1-yl)alkyl!pyran-2-ones by a novel synthesis is described where .alpha.-metalated N,N-disubstituted acetamide is converted in seven operations to the desired products, and specifically, a process for preparing (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N, 4-diphenyl-1- 2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl!-1H-pyrrol e-3-carboxamide, as well as other valuable intermediates used in the processes and prodrugs which are bioconverted to hypolipidemic and hypocholesterolemic agents and pharmaceutical compositions of the same.
Claims8
A compound of Formula VI ##STR28## wherein R.sup.8 or R.sup.9 is independently alkyl of from one to ten carbon atoms,
- cyclopropyl,
- cyclobutyl,
- cyclopentyl,
- cyclohexyl,
- benzyl or
- phenyl or
- R.sup.8 and R.sup.9 together are
- --(CH.sub.2).sub.4 --,
- --(CH.sub.2).sub.5 --,
- --(CH(R.sup.10)--CH.sub.2).sub.3 --,
- --(CH(R.sup.10)--CH.sub.2).sub.4 --,
- --(CH(R.sup.10)--(CH.sub.2).sub.2 --CH(R.sup.10))--,
- --(CH(R.sup.10)--(CH.sub.2).sub.3 --CH(R.sup.10))--,
- --CH.sub.2 --CH.sub.2 --O--CH.sub.2 --CH.sub.2 --,
- --CH(R.sup.10)--CH.sub.2 --O--CH.sub.2 --CH.sub.2 --,
- --CH(R.sup.10)--CH.sub.2 --O--CH.sub.2 --CH(R.sup.10)--,
- wherein R.sup.10 is alkyl of from one to four carbon atoms provided R.sup.8 and R.sup.9 are not both methyl;
- and
- R.sup.11 or R.sup.12 is independently alkyl of from one to three carbon atoms or phenyl or
- R.sup.11 and R.sup.12 are taken together as --(CH.sub.2).sub.n -- wherein n is 4 or 5.
Dependencies are inferred from the claim text.