Abstract: A method of making an amino-alkylenediol and intermediate compounds useful in the method is disclosed. The method includes preparing a first intermediate compound comprising an aminoalkylene diol wherein a protecting group is linked to the amino functionality, and optionally, preparing a second intermediate compound comprising a salt of the first intermediate compound. The first intermediate compound has the structure wherein R is a divalent alkylene radical having from 2 to 20 carbon atoms, X and Y are independently a divalent linking moiety or a single bond, and Z is a protecting group. The second intermediate compound has the structure wherein R is a divalent alkylene radical having from 2 to 20 carbon atoms, X and Y are independently a divalent linking moiety or a single bond, TsO? is toluene sulfonate, and Z is a protecting group.

Abstract: The present invention provides a process for producing a N4-acyl-5?-deoxy-5-fluorocytidine compound of the formula: where R2 is alkyl, cycloalkyl, aralkyl, aryl, or alkoxy.

Abstract: The present invention provides a process for producing a N4-acyl-5?-deoxy-5-fluorocytidine compound of the formula: where R2 is alkyl, cycloalkyl, aralkyl, aryl, or alkoxy.

Abstract: Intermediates of Formula (III) ##STR1## wherein P.sup.1 is hydrogen or an amino-protecting group, R is lower alkyl, allyl or aralkyl, and Z is hydrogen, lower alkyl, aryl or aralkyl; and Formula (VI) ##STR2## wherein P.sup.1 is hydrogen or an amino-protecting group, P.sup.2 is an amino protecting group, and Z is hydrogen, lower alkyl, aryl or aralkyl, are useful in a novel process for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol (ganciclovir). The mono-L-valine ester of ganciclovir and its pharmaceutically acceptable salts are of value as antiviral agents with improved absorption.

Abstract: Process and novel intermediates for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol ganciclovir) and its pharmaceutically acceptable salts. The present process and monoester intermediates provide for mono-esterification by an L-valine derivative, resulting in a monocarboxylate-monovalinate which is then selectively hydrolyzed under basic or enzymatic conditions to give the monovaline ester of ganciclovir in high yield and purity. These products are of value as antiviral agents with improved absorption.

Abstract: A method of preparing 2-?2-{?3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate comprises contacting (6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid or an activated derivative of (6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid with ?3-(1H-benzimidazol-2-yl)propyl!methylamine to form N-?3-(1H-benzimidazol-2-yl) propyl!-2-(6-fluoro-2-hydroxy-1-isopropyl-1,2,3 ,4-tetrahydronaphthalen-2- yl)-N-methylacetamide, reducing this to 2-?2-{?3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1, 2,3,4-tetrahydronaphthalen-2-ol, and treating the 2-?2-{?3-(1H-benzimidazol-2-yl) propyl!-methylamino}ethyl!-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthal en-2-ol with methoxyacetic acid or an activated derivative of methoxyacetic acid.

Abstract: A method of preparing 2-?2-{?3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate comprises contacting 6-fluoro-1-isopropyl-3,4-dihydro-1H-naphthalen-2-one with the anion of acetonitrile in an aprotic polar solvent; contacting ?3-(1H-benzitidazol-2-yl)propyl!methylamine with the thus-formed (6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetonit rile in the presence of hydrogen and a hydrogenation catalyst, followed by contacting the thus-formed 2-?2-{?3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1,2,3,4-tetrahydronaphthalen-2-ol with methoxyacetic acid or an activated derivative of methoxyacetic acid. The invention is particularly applicable to the preparation of mibefradil, (1S,2S)-2-?2-{?3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro- 1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate, and its dihydrochloride salt.