1345879-87-9

Usage

Uses

Used in Pharmaceutical Industry:
Levosalbutamol is used as a bronchodilator for the treatment of symptoms associated with asthma and chronic obstructive pulmonary disease (COPD). As a beta2-agonist, it works by relaxing the muscles in the airways, allowing for easier breathing and providing relief from acute symptoms of bronchospasm. Its rapid onset of action and effectiveness in managing respiratory conditions make it a valuable medication for improving the quality of life for individuals with breathing difficulties.

Upstream product

• 67843-74-7 (S)-epichlorohydrin 
• 104-88-1 4-chlorobenzaldehyde 

Downstream Products

• 1345879-82-4 (S)-(E,Z)-5-((4-chlorobenzylideneamino)methyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one 
• 1345879-85-7 (S)-(E,Z)-N-4-chlorobenzylidene-1-(oxiran-2-yl)methanamine 
• 1414932-72-1 4-{4-[(S)-5-[(((4-chlorophenyl)methylene)amino)methyl]-2-oxo-1,3-oxazolidin-3-yl]phenyl}-morpholin-3-one 
• 1450915-99-7 4-{4-[(R)-5-[(((4-chlorophenyl)methylene)amino)methyl]-2-oxo-1,3-oxazolidin-3-yl]phenyl}-morpholin-3-one 

Relevant academic research and scientific papers

Incorporation of a chiral gem-disubstituted nitrogen heterocycle yields an oxazolidinone antibiotic with reduced mitochondrial toxicity

gem-Disubstituted N-heterocycles are rarely found in drugs, despite their potential to improve the drug-like properties of small molecule pharmaceuticals. Linezolid, a morpholine heterocycle-containing oxazolidinone antibiotic, exhibits significant side effects associated with human mitochondrial protein synthesis inhibition. We synthesized a gem-disubstituted linezolid analogue that when compared to linezolid, maintains comparable (albeit slightly diminished) activity against bacteria, comparable in vitro physicochemical properties, and a decrease in undesired mitochondrial protein synthesis (MPS) inhibition. This research contributes to the structure-activity-relationship data surrounding oxazolidinone MPS inhibition, and may inspire investigations into the utility of gem-disubstituted N-heterocycles in medicinal chemistry.

A convenient synthesis of the antibacterial agent linezolid

Starting with 3,4-difluorobenzoic acid (8) and (S)-epichlorohydrin (13) a convergent synthesis of linezolid (1) was developed that is attractive for large scale preparation of the drug. The synthetic strategy involves a 1+3 cycloaddition reaction between the chiral epoxide 11 (prepared from 13) and isocyanate 3 (obtained from 8) that was generated in situ by a Curtius rearrangement. The resulting Schiff base precursor of linezolid (12) crystallized from the reaction mixture and was readily converted to linezolid by an acid-catalyzed hydrolysis followed by an acetylation.

PROCESS FOR OBTAINING RIVAROXABAN AND INTERMEDIATE THEREOF

This invention relates to a procedure for obtaining a thiophene-2-carboxamide compound, specifically rivaroxaban, which comprises the (i) fragmentation of the N═C bond of a compound of formula 23 where R1 is selected among hydrogen, halogen, and (C1-C6)alkyl; and (ii) acylation of the resulting intermediate with 5-chloro-tiofen-2-carbonyl chloride in a solvent medium, in the presence of a base. The invention also relates to the compounds of formula 23 and their use in the obtention of rivaroxaban.

PROCESSES FOR PREPARING RIVAROXABAN

Processes and intermediates for preparing rivaroxaban, and analogs and derivatives thereof, and pharmaceutically acceptable salts of each of the foregoing, are described herein.

A PROCESS FOR THE PREPARATION OF RIVAROXABAN BASED ON THE USE OF (S)-EPICHLOROHYDRIN

The invention relates to the stereoisomers of 4-{4-[(S/R)-5-[(((aryl)methylene)- amino)methyl]-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-ones described by the chemical formulae (S)-(9) and (R)-(9). The optical isomer of compound (9) with the (S)- configuration is industrially applicable for the manufacture of the antithrombotic drug rivaroxaban (1). The new preparation process of rivaroxaban comprises a reaction of (S)-1- chloro-3-(((aryl)methylene)amino)propan-2-ols (S)-(14) with alkyl 4-(3-oxomorpholine-4- yl)phenylcarbamates (15) providing the key intermediate (S)-(9), which is further subjected to hydrolytic deprotection and subsequent acylation, producing rivaroxaban. The commercially available (S)-epichlorohydrin has been conveniently used as the chiral building block for the production of the key intermediate.

PROCESS FOR OBTAINING RIVAROXABAN AND INTERMEDIATE THEREOF

This invention relates to a procedure for obtaining a thiophene-2-carboxamide compound, specifically rivaroxaban, which comprises the (i) fragmentation of the N=C bond of a compound of formula 23 where R1 is selected among hydrogen, halogen, and (C1-C6)alkyl; and (ii) acylation of the resulting intermediate with 5-chloro-tiofen-2-carbonyl chloride in a solvent medium, in the presence of a base. The invention also relates to the compounds of formula 23 and their use in the obtention of rivaroxaban.

PROCESSES FOR PREPARING LINEZOLID

Processes and intermediates for preparing linezolid, and pharmaceutically acceptable salts thereof, are described herein.