1,6- diazabicyclo [3,2,1] octan-7-one derivatives and their use in the treatment of bacterial infections

Abstract

Compounds of Formula (I), their preparation and use in preventing or treating bacterial infections are disclosed.

1 . A compound which is tetrabutylammonium salt of (2S,5R)-2-[(6-sulfooxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-methyloxycarbamoyl]-(2S)-pyrrolidine-1-carboxylic acid tert-butyl ester. 
     
     
         2 . A method of preparing (2S,5R)-7-oxo-N-[(2S)-pyrrolidin-2-ylmethyloxy]-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide, comprising reacting tetrabutylammonium salt of (2S,5R)-2-[(6-sulfooxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-methyloxycarbamoyl]-(2S)-pyrrolidine-1-carboxylic acid tert-butyl ester with trifluoroacetic acid. 
     
     
         3 . The method according to  claim 2 , wherein the reacting step is carried out in the presence of dichloromethane. 
     
     
         4 . The method according to  claim 2 , wherein the reacting step is carried out at a temperature of −10° C. 
     
     
         5 . A method of preparing (2S,5R)-7-oxo-N-[(2S)-pyrrolidin-2-ylmethyloxy]-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide, comprising:
 (a) reacting (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid with 2-aminooxymethyl-(S)-pyrrolidine-1-carboxylic acid t-butyl ester to obtain (2S,5R)-2-[(6-benzyloxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-methyloxycarbamoyl]-(2S)-pyrrolidine-1-carboxylic acid tert-butyl ester,   (b) hydrogenating the (2S,5R)-2-[(6-benzyloxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-methyloxycarbamoyl]-(2S)-pyrrolidine-1-carboxylic acid tert-butyl ester to obtain (2S,5R)-2-[(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-methyloxycarbamoyl]-(2S)-pyrrolidine-1-carboxylic acid tert-butyl ester,   (c) sulfonating the (2S,5R)-2-[(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-methyloxycarbamoyl]-(2S)-pyrrolidine-1-carboxylic acid tert-butyl ester, followed by tetrabutylammonium salt formation to obtain tetrabutylammonium salt of (2S,5R)-2-[(6-sulfooxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-methyloxycarbamoyl]-(2S)-pyrrolidine-1-carboxylic acid tert-butyl ester, and   (d) deprotecting the tetrabutylammonium salt of (2S,5R)-2-[(6-sulfooxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-methyloxycarbamoyl]-(2S)-pyrrolidine-1-carboxylic acid tert-butyl ester to obtain the (2S,5R)-7-oxo-N-[(2S)-pyrrolidin-2-ylmethyloxy]-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide.   
     
     
         6 . The method according to  claim 5 , wherein step (a) is carried out in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, 1-hydroxybenzotriazole and N-methylmorpholine. 
     
     
         7 . The method according to  claim 5 , wherein the hydrogenating in step (b) is carried out in the presence of palladium on carbon as catalyst. 
     
     
         8 . The method according to  claim 5 , wherein the sulfonating in step (c) is carried out in the presence of sulfur trioxide-dimethylformamide complex. 
     
     
         9 . The method according to  claim 5 , wherein the tetrabutylammonium salt formation in step (c) is carried out in the presence of tetrabutylammonium acetate. 
     
     
         10 . The method according to  claim 5 , wherein the deprotecting in step (d) is carried out in the presence of trifluoroacetic acid.