1380110-39-3

Upstream product

• 100-39-0 benzyl bromide 
• 1380110-38-2 tert-butyl [(2R,3S)-2-(aminomethyl)-1-(2,4-dimethoxybenzyl)-4-oxoazetidin-3-yl]carbamate 
• 1380112-29-7 CH₄O₃S*C₂₀H₂₀N₂O₃ 
• 530-62-1 1,1'-carbonyldiimidazole 
• 501-30-4 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one 
• 1380112-32-2 C₁₈H₁₄O₈*C₁₈H₂₇N₃O₅ 
• 15771-06-9 5-benzyloxy-2-hydroxymethyl-4H-pyran-4-one 
• 1445727-47-8 C₂₄H₂₂N₄O₄ 
• 1380109-80-7 2-(aminomethyl)-1,5-bis(benzyloxy)-1,4-dihydropyridin-4-one 
• 1380109-77-2 5-(benzyloxy)-1-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one 

Downstream Products

• 1380110-32-6 2-((((Z)-2-(((2R,3S)-2-((3-((1,5-bis-(benzyloxy)-4-oxo-1,4-dihydropyridin-2-yl)methyl)ureido)-methyl)-4-oxoazetidin-3-yl)amino)-1-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)-2-oxoethylidene)-amino)oxy)-2-methylpropanoic acid tert-butyl ester 
• 1380110-33-7 (2R,3S)-2-((3-((1,5-bis(benzyloxy)-4-oxo-1,4-dihydropyridin-2-yl)methyl)ureido)methyl)-3-((Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetamido)-4-oxoazetidine-1-sulfonic acid 
• 1380110-40-6 tert-butyl ((2R,3S)-2-((3-((1,5-bis-(benzyloxy)-4-oxo-1,4-dihydropyridin-2-yl)methyl)ureido)-methyl)-4-oxoazetidin-3-yl)carbamate 
• 1380110-42-8 1-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)-methyl)-3-((1,5-bis(benzyloxy)-4-oxo-1,4-dihydropyridin-2-yl)methyl)urea trifluoroacetic acid salt 

Relevant academic research and scientific papers

Enabled Process to Synthesize Monobactam 1 for Early Development

An efficient process to synthesize Monobactam 1 from intermediates 2, 3, and 4 was developed. The process was initially enabled to deliver 500 g of 1 for exploratory toxicity studies and further improved to facilitate kilogram-scale production of the active pharmaceutical ingredient with enhanced quality and throughput. Highlights of the process encompass utilizing 1,1′-carbonyldiimidazole to construct a urea linker with good selectivity, oxidative cleavage to remove a 2,4-dimethoxybenzyl protecting group, two activation methods to form an amide bond, a high yielding reaction to introduce N-sulfonic moiety, and a global deprotection to remove all protecting groups. Practical procedures were developed to isolate intermediates en route by adding a concentrated substrate to antisolvents to obtain filterable amorphous solids with partial purification. Amberchrom CG161M resin was applied not only as a "resin-capture-release" tool to remove the bulk amount of water but also as an effective method to purify 1. Finally, a process isolating 1 pentahydrate (1·5H2O) as a crystalline solid from the acidic aqueous solution was developed based on zwitterionic crystallization methodology.

MONOBACTAMS

The present invention is directed to a new class of monobactam derivatives and their use for treating bacterial infections.