Gamal Shams

US Patent:

47375043, Apr 12, 1988

Filed:

Jul 25, 1986

Appl. No.:

6/890490

Inventors:

Duane D. Miller - Worthington OH
Dennis R. Feller - Columbus OH
Michael T. Clark - West Chester PA
Adeboye Adejare - Kensington MD
Karl J. Romstedt - Columbus OH
Gamal Shams - Columbus OH

Assignee:

Ohio State University Research Foundation - Columbus OH

International Classification:

A61K 3147
C07D21720

US Classification:

514307

Abstract:

The present invention relates to novel 5-fluoro- and 8-fluoro-trimetoquinol compounds of the general formula I wherein X. sub. 1 =F,X. sub. 2 =H or X. sub. 1 =H,X. sub. 2 =F ##STR1## The present invention also relates to a process for making the 5-fluoro- and 8-fluoro-trimetoquinol compounds by condensation of an appropriately substituted phenethylamine to afford an appropriately substituted phenethylacetamide compound. The amides are cyclized to give appropriately substituted intermediate dihydroisoquinolines. Without isolation, the dihydroisoquinolines are reduced to give appropriately substituted tetrahydroisoqinolines. The hydrochloride salts of tetrahydroisoqinolines are prepared and subjected to hydrogenolysis, to give the fluorine substituted trimetoquinol compounds of the present invention. The present invention also encompasses the preparation of the phenethylamines by reducing appropriately substituted benzylcyanides and to the preparation of an intermediate benzylcyanide compound by converting a fluorine substituted methoxyphenol compound, under aminomethylation conditions into a N, N-dimethyl-4-hydroxy-3-methoxy-5-fluorobenzylamine. The benzylamine is converted to benzylnitrile and a functional group shuffle is carried out which yields the appropriately substituted benzylcyanide compound.

US Patent:

48554766, Aug 8, 1989

Filed:

Mar 14, 1988

Appl. No.:

7/167336

Inventors:

Duane D. Miller - Worthington OH
Dennis R. Feller - Columbus OH
Michael T. Clark - West Chester PA
Adeboye Adejare - Kensington MD
Karl J. Romstedt - Columbus OH
Gamal Shams - Columbus OH

Assignee:

Ohio State University Research Foundation - Columbus OH

International Classification:

C07C12000
C07C12166

US Classification:

558410

Abstract:

The present invention relates to novel 5-fluoro- and 8-fluoro-trimetoquinol compounds of the general formula I wherein X. sub. 1 =F, X. sub. 2 =H or X. sub. 1 =H, X. sub. 2 =F ##STR1## The present invention also relates to a process for making the 5-fluoro- and 8-fluoro-trimetoquinol compounds by condensation of an appropriately substituted phenethylamine to afford an appropriately substituted phenlethylacetamide compound. The amides are cyclized to give appropriately substituted intermediate dihydroisoquinolines. Without isolation, the dihydroisoquinolines are reduced to give appropriately substituted tetrahydroisoquinolines. The hydrochloride salts of tetrahydroisoquinolines are prepared and subjected to hydrogenolysis, to give the fluorine substituted trimetoquinol compounds of the present invention. The present invention also encompasses the preparation of the phenethylamines by reducing appropriately substituted benzylcyanides and to the preparation of an intermediate benzylcyanide compound by converting a fluorine substituted methoxyphenol compound, under aminomethylation conditions into a N-N-dimethyl-4-hydroxy-3-methoxy-5-fluorobenzylamine. The benzylamine is converted to benzylnitrile and a functional group shuffle is carried out which yields the appropriately substituted benzylcyanide compound.