Merck Sharp + Dohme Corp.

Calixa Therapeutics, Inc.

Kristos Adrian Moshos

Valdas Jurkauskas

You Seok Hwang

Manuel Scanu

Giovanni Fogliato

Michele Benotti

Nicole Miller Damour

Joseph Terracciano

Sudhakar Devidasrao Garad

Youchu Wang

Jian-Qiao Gu

Pradip M Pathare

Jason Woertink

Yisheng Yang

Carlos Lopez

Lisa Duong

Sanjay Mudur

Asli Ovat

Described herein are crystalline forms of a compound of formula (III'), including toluene solvates of TATD-CLE, as well as processes for the preparation thereof and use thereof in the preparation of cephalosporin compounds such as ceftolozane.

Intermediates in the synthesis of cephalosporin compounds

This disclosure provides methods of making certain 7-aminocephem derivatives useful in the manufacture of cephalosporin antibiotic compounds.

7-aminocephem derivative compounds

Described herein are crystalline forms of a compound of formula (II&#x393;), including toluene solvates off A TD-CLE, as well as processes for the preparation thereof and use thereof in the preparation of cephalosporin compounds such as ceftolozane. Provided herein is a crystalline form of a compound of formula (II&#x393;): wherein X is CI, Br, or I; and R1 and R2 are each independently an oxygen protecting group; processes for making the crystalline form, and use of said form in the synthesis of antibacterial cephalosporins such as ceftolozane.

Described herein are methods for the manufacture of ceftolozane and related compounds, as well as compositions comprising the same.

Synthesis of cephalosporin compounds

Thiadiazolyl-oximinoacetic acid derivatives have been synthesized, which are useful in the manufacture of cephalosporin antibiotic compounds. Compound (1) (TATD) is commercially available (CAS No. 76028-96-1). It has now been discovered that the thiadiazolyl-oximinoacetic acid derivative compound (1) (TATD) can be prepared from dimethyl malonate (SM 1, CAS No. 108-59-8) according to methods described herein. The methods provide products having desirable purity.

Thiadiazolyl-oximinoacetic acid derivative compounds

Pyrazolyl carboxylic acid and pyrazolyl urea derivatives have been synthesized, which are useful in the manufacture of cephalosporin antibiotic compounds.

Pyrazolyl carboxylic acid and pyrazolyl urea derivative compounds

This disclosure relates to salt forms of ceftolozane, processes for making these salt forms, and compositions comprising the same. Also disclosed are stabilized compositions of ceftolozane. Provided herein are salt forms of ceftolozane, processes for making these salt forms and compositions comprising the same. The salt forms provided herein include ceftolozane bromide, ceftolozane edisylate, ceftolozane mesylate, ceftolozane chloride, ceftolozane sulfate, ceftolozane maleate, ceftolozane phosphate, and ceftolozane ketoglutarate.

Salt forms of ceftolozane

This disclosure relates to an improved synthesis of cephalosporin antibiotic compounds such as ceftolozane, and compositions and methods of use thereof. Thiadiazolyl-oximinoacetic acid compounds such as TATD can be reacted to yield the activated thiadiazolyl-oximinoacetic acid methanesulfonate ester compounds useful in the manufacture of cephalosporin antibiotic compounds.

Reactions of thiadiazolyl-oximinoacetic acid derivative compounds

Novel solid forms of ceftolozane are described, as well as methods for the preparation and use of these solid forms.

Growing community of inventors

Belmont, MA, United States of America

Kristos Adrian Moshos