82626-48-0

Basic information

• Product Name: Zolpidem
• Synonyms: 2-a)pyridine-3-acetamide,2-(4-methylphenyl)-n,n,6-trimethyl-imidazo(;N,N,6-Trimethyl-2-p-tolylimidazo[1,2-a]pyridine-3-acetamide;N,N-Dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide;SL-80.0750;N,N,6-TRIMETHYL-2-(4-METHYLPHENYL)-IMIDAZO[1,2-A]PYRIDINE-3-ACETAMIDE;N,N,6-TRIMETHYL-2-(4-METHYLPHENYL)-IMIDAZO[1,2-A]PYRIDINE-3-ACETAMIDE HEMITARTRATE;N,N,6-TRIMETHYL-2-(4-METHYLPHENYL)IMIDAZO[1,2-A]PYRIMIDINE-3-ACETAMIDE;ZOLPIDEM
• CAS NO: 82626-48-0
• Molecular Formula: C₁₉H₂₁N₃O
• Molecular Weight: 307.39
• Product Categories: Pyridines derivates;(intermediate of zolpidem);Zolpidem;Amines;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Isotopically Labeled Pharmaceutical Reference Standard
• Mol File: 82626-48-0.mol
• Article Data: 43

Chemical Properties

• Melting Point: 189-191°C
• Flash Point: 9℃
• Appearance: white/solid
• Density: 1.12 g/cm³
• Refractive Index: 1.601
• Storage Temp.: Store at RT
• Solubility: 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: 0.3 mg/mL
• PKA: 6.2(at 25℃)
• Water Solubility: <10mg/L(room temperature)
• CAS DataBase Reference: Zolpidem(CAS DataBase Reference)
• NIST Chemistry Reference: Zolpidem(82626-48-0)
• EPA Substance Registry System: Zolpidem(82626-48-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution
• WGK Germany: 3
• RTECS: NJ5109750
• Hazardous Substances Data: 82626-48-0(Hazardous Substances Data)

Usage

Description

Zolpidem, marketed under the brand names Ambien and Stilnox, is a non-benzodiazepine hypnotic belonging to the imidazopyridine class. It exhibits specific agonist activity at type 1 benzodiazepine receptors and is characterized by its off-white solid appearance. Zolpidem is a selective non-benzodiazepine GABAA receptor agonist, acting as a sedative and hypnotic. It is structurally distinct from classical benzodiazepines, lacking their side-effects and abuse potential. Zolpidem is also a controlled substance due to its depressant effects.

Uses

Used in Pharmaceutical Industry:
Zolpidem is used as a sedative and hypnotic for the treatment of insomnia and other sleep disorders. Its high selectivity for the α1 subunit of the benzodiazepine binding site on the GABAA receptor complex contributes to its rapid onset of action and good bioavailability. It has a short elimination half-life, making it suitable for sleep maintenance.
Used in Research and Forensic Applications:
Zolpidem is utilized as an analytical and certified reference material for research purposes. It aids in the development of new treatments for insomnia and sleep disorders, as well as in forensic applications for the detection and analysis of the substance in biological samples.
Used as a Pre-operative Sedative:
Zolpidem is currently being studied for its potential use as a pre-operative sedative, providing calmness and relaxation before surgical procedures.

InChI:InChI=1/C19H21N3O/c1-13-5-8-15(9-6-13)19-16(11-18(23)21(3)4)22-12-14(2)7-10-17(22)20-19/h5-10,12H,11H2,1-4H3

Upstream product

• 258273-50-6 methyl 2-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)acetate 
• 124-40-3 dimethyl amine 
• 193979-47-4 ethyl 6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetate 
• 62285-47-6 2-diazo-N,N-dimethyl-acetamide 
• 88965-00-8 6-methyl-2-(4-methyl-phenyl)-imidazo[1,2-a]pyridine 
• 768398-03-4 6-methyl-3-cyanomethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine 
• 189005-44-5 6-methyl-2-(4-methylphenyl)-imidazo<1,2-a>pyridine-3-acetic acid 
• 851972-89-9 2-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yl)-ethanol 
• 80-62-6 methacrylic acid methyl ester 
• 1603-41-4 (5-methyl-pyridin-2-yl)amine 
• 619-41-0 4-(bromoacetyl)toluene 
• 695-34-1 2-Amino-4-methylpyridine 
• 5720-05-8 4-methylphenylboronic acid 
• 400777-11-9 6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridine-3-carbaldehyde 

Downstream Products

• 30223-73-5 (R,S)-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine 
• 189005-44-5 6-methyl-2-(4-methylphenyl)-imidazo<1,2-a>pyridine-3-acetic acid 
• 118026-14-5 N,N,6-trimethyl-2-(4-methylphenyl)-imidazo[1,2-α]pyridine-3-α-hydroxyacetamide 

Relevant articles and documents

Structural and thermal characterization of zolpidem hemitartrate hemihydrate (Form E) and its decomposition products by laboratory x-ray powder diffraction

The crystal structure of zolpidem hemitartrate hemihydrate (I, Form E) has been solved from high-resolution laboratory powder diffraction data. It crystallizes in the orthorhombic P212121 space group with a=22.4664(6)?, b=26.0420(7)?, and c=7.4391(1)?. Protonation of zolpidem molecules could not be unambiguously determined. Thermal stability of Form E has been investigated by TG-DTA and in situ by temperature resolved X-ray powder diffraction. Water loss occurs between 508C≤t≤1008C while structure decomposition commences at approximately 120°C yielding zolpidem tartrate (II) and pure zolpidem base (III) in approximately equimolar amounts. Crystal structures of II and III have been solved simultaneously from a single powder pattern of thermally decomposed I. Zolpidem tartrate crystallizes in the orthorhombic P212121 space group with a=19.9278(8)?, b=15.1345(8)?, and c=7.6246(2)? (at 140°C). Zolpidem base crystallizes in the orthorhombic Pcab space group with a=9.9296(4)?, b=18.4412(9)?, and c=18.6807(9)? (at 140°C). In the reported crystal structures zolpidem molecules form stacks through π-π interaction or dipole-dipole interactions while tartrate moieties, if present, form hydrogen bonded chains. Water molecule in I forms a hydrogen bond to the imidazole nitrogen atom of the zolpidem molecule. Free space in the crystal structure of I could allow for the additional water molecules and thus a variable water content.

Zolpidem preparation method

The invention belongs to the technical field of drug synthesis, and provides a zolpidem preparation method which comprises the following steps: by taking SM-1 as a starting material, Rh (trop2N) (PPh3) as a catalyst and MMA as a hydrogen acceptor, carrying out catalytic dehydrogenation coupling reaction on the starting material, the catalyst and dimethylamine, and carrying out acid dissolution and alkali precipitation refining to obtain a product with higher purity. Compared with the prior art, the zolpidem preparation process has the advantages that the process route can be obviously shortened, and the preparation process is suitable for industrial production.

Preparation method of zolpidem

The invention discloses a preparation method of a zolpidem intermediate. In the process of preparing the zolpidem intermediate N, N, 6-trimethyl-2-(4-methylphenyl)-imidazo [1, 2-alpha] pyridine-3-acetamide hydrochloride by reducing N, N, 6-trimethyl-2-(4-methylphenyl)-imidazo [1, 2-alpha] pyridine-3-acetamide hydrochloride, through process optimization and parameter adjustment, by using a 10% palladium-carbon catalyst and combining the reaction condition of hydrogen pressure of 0.02-0.09 MPa, the conversion effect of the N, N, 6-trimethyl-2-(4-methylphenyl)-imidazo [1, 2-alpha] pyridine-3-chloroacetamide hydrochloride is promoted, side reactions and impurities are reduced, the product yield is increased, the problem of low product synthesis yield in the process of preparing N, N, 6-trimethyl-2-(4-methylphenyl)-imidazo [1, 2-alpha] pyridine-3-acetamide hydrochloride through reduction reaction in zolpidem production is solved, and the production cost of zolpidem tartrate is reduced.

Study on a three-step rapid assembly of zolpidem and its fluorinated analogues employing microwave-assisted chemistry

We developed an efficient microwave-assisted three-step synthesis of zolpidem and its fluorinated analogues 1-3. The procedure relays on the utilization of easily accessible and inexpensive starting materials. Our protocol shows superior performance in terms of yield and purity of products, compared to conventional heating systems. Notably, the total time needed for reaction accomplishment is significantly lower comparing to oil bath heating systems. Finally, we have performed a detailed study on the preparation of zolpidem tartrate salt I, and we assessed its particle-sizes using a polarizing microscope. Our goal was to select the appropriate method that generates the acceptable particle-size, since the solid-size directly influences solubility in biological fluids and further bioavailability. We believe that the disclosed procedure will help to produce a lab-scale quantity of zolpidem and its fluorinated derivatives 1-3, as well as zolpidem tartrate salt I, with suitable fine-particle size for further biological experimentation.