Method of preparing (+)-1,4-dihydro-7-[(3s,4s)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid

Abstract

Methods of preparing (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid are disclosed. Also provided are pharmaceutical compositions comprising (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, and methods of treatment using such compositions.

1 - 44 . (canceled) 
     
     
         45 . A single unit dosage form comprising a composition consisting essentially of at least 99.95% (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and less than 0.05% (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-amino-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid based on total weight of the composition. 
     
     
         46 . The single unit dosage form of  claim 45 , wherein the composition is a lyophilized powder. 
     
     
         47 . The single unit dosage form of  claim 45  comprising sufficient (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid to permit administration of doses of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid within the range of about 10-100 mg/m 2 . 
     
     
         48 . The single unit dosage form of  claim 45 , wherein the dosage form is for intravenous administration. 
     
     
         49 . The single unit dosage form of  claim 45  comprising about 1-50 mg of the composition. 
     
     
         50 . The single unit dosage form of  claim 49  comprising about 25 mg of the composition. 
     
     
         51 . The single unit dosage form of  claim 49  further comprising methanesulfonic acid. 
     
     
         52 . The single unit dosage form of  claim 51  further comprising sorbitol. 
     
     
         53 . The single unit dosage form of  claim 51  suitable for reconstitution with water to provide a liquid dosage form for intravenous administration.