Eli Lilly and Company

Dowelanco

David D Wirth

Gregory Alan Stephenson

James M Greene

Holly M Hankins

Gary E Lord

Robert M Metzler

The invention provides Form II dirithromycin, a novel polymorph of dirithromycin. Also disclosed are the acetone, 1-butanol, 1-propanol, and 2-propanol solvates of dirithromycin, which provide an efficient means for preparing and isolating Form II. Processes for preparing and isolating Form II dirithromycin from these solvates or from Form I dirithromycin are provided. A process for obtaining Form II dirithromycin from non-solvated dirithromycin is also provided. Another aspect of the invention is an improved tablet containing Form II dirithromycin as the active ingredient.

Process for preparing crystal forms and solvates of dirithromycin

A process for the preparation of 1-(2'-deoxy-2', 2'-difluoro-D-ribo-pentofuranosyl)-cytosine (VI) from 2-deoxy-2,2-difluoro-.beta.-D-ribo-pentopyranose (I). The process uses a tritylation reaction (Step 3) for preparing 2-deoxy-2,2-difluoro-5-O-triphenylmethyl-ribo-pentofuranose (II) as a key intermediate. The 1-(2'-deoxy-2', 2'-difluoro-D-ribo-pentofuranosyl)-cytosine (VI) is an antiviral and anti-cancer agent.

Process for the preparation of

A process for producing intermediate compounds 2-deoxy 2,2-difluoro-.beta.-D-ribo-pentopyranose (III) from 3,3-difluoro-4,5,6-O-trihydroxy-5,6-O-(1-ethylpropylidene)hexene (I). The process of preparing intermediate compound (I) involves reacting D-glyceraldehyde pentanide with an organometallic complex of 3-bromo-3,3-difluoropropene. The process of preparing intermediate compound (III) involves ozonolysis and then hydrolysis. The intermediate compounds (I) and (III) are used in the preparation of 2'-deoxy-2',2'-difluorocytidine which is an antiviral agent.

A process for the preparation of 1-(2'-deoxy-2',2'-difluoro-D-ribo-pentofuranosyl)-cytosine (VI) from 2-deoxy-2,2-difluoro-.beta.-D-ribo-pentopyranose (I). The process uses a tritylation reaction (Step 3) for preparing 2-deoxy-2,2-difluoro-5-O-triphenylmethyl-ribo-pentofuranose (II) as a key intermediate. The 1-(2'-deoxy-2',2'-difluoro-D-ribo-pentofuranosyl)-cytosine (VI) is an antiviral and anti-cancer agent.

Preparation of

The present invention is directed toward a process of treating crude dinitroaniline with an aqueous sulfite solution as a method of stabilizing the herbicide against formation of nitrosamines and of reducing impurities therein.

Process for treating dinitroanilines with sulfite to reduce impurities

An improvement in the process of preparing ceftazidime pentahydrate from ceftazidime dihydrobromide which comprises commingling a secondary-amine-type ion-exchange resin such as Amberlite LA-2 in a water-immiscible organic solvent with an aqueous solution of the dihydrobromide, stirring the mixture while maintaining a pH at or below about 6.0 and isolating ceftazidime pentahydrate from the aqueous layer. This process provides significantly higher yields of the pentahydrate than previously could be obtained from the dihydrobromide.

Process for preparing ceftazidime pentahydrate

The present invention provides a process for preparing a 3-iodomethyl cephalosporin by treating a bis(trialkylsilyl)-7-amino-4-carboxylic acid-3-substituted cephalosporin derivative with a trialkylsilyl iodide derivative.

Growing community of inventors

Lafayette, IN, United States of America

David D Wirth