91402-80-1

Usage

Uses

(R) enantiomer of Lorazepam (L469850).

Upstream product

• 2848-96-6 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2-oxo-2H-1,4-benzodiazepin-3-yl acetate 
• 846-49-1 lorazepam 
• 14405-03-9 2-chloroacetamido-2’,5-dichlorobenzophenone 
• 2958-36-3 (2-amino-5-chloro-phenyl)-(2-chloro-phenyl)-methanone 
• 125534-53-4 lorazepam acetone solvate 
• 2955-37-5 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepine-2-one-4-oxide 
• 848-75-9 lormetazepam 
• 89722-85-0 Trifluoro-acetic acid 7-chloro-5-(2-chloro-phenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl ester 

Downstream Products

• 134051-36-8 Benzoic acid 7-chloro-5-(2-chloro-phenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl ester 
• 18878-24-5 3-O-ethyllorazepam 
• 130753-96-7 2-Methyl-3-nitro-benzoic acid 7-chloro-5-(2-chloro-phenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl ester 
• 71107-65-8 lorazepam-β-phenyl-propionate 
• 71107-66-9 lorazepam-α-methyl-β-phenyl-propionate 
• 4306-26-7 7-chloro-5-(2-chloro-phenyl)-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one 
• 82384-75-6 (7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one)AuCl₃ 
• 130753-89-8 (S)-2-(6-Methoxy-naphthalen-2-yl)-propionic acid (S)-7-chloro-5-(2-chloro-phenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl ester 
• 130754-08-4 (S)-2-(6-Methoxy-naphthalen-2-yl)-propionic acid (R)-7-chloro-5-(2-chloro-phenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl ester 

Relevant academic research and scientific papers

New crystal form of lorazepam, preparation method and pharmaceutical applications thereof

The invention relates to a new crystal form for preparing lorazepam, a preparation method and pharmaceutical applications thereof, wherein specifically the lorazepam crystal has diffraction peaks at about 12.17 DEG, about 14.15 DEG, about 15.27 DEG, about 16.84 DEG, about 17.91 DEG and about 20.81 DEG in a powder X-ray diffraction pattern represented by a 2[theta] angle by using Cu-Kalpha radiation, for example, the crystal has diffraction peaks at about 7.93 DEG, about 9.04 DEG, about 12.17 DEG, about 14.15 DEG, about 15.27 DEG, about 16.84 DEG, about 17.91 DEG, about 20.81 DEG, about 21.44 DEG and about 26.38 DEG. The invention further provides a preparation method of the new crystal of larazepam, and pharmaceutical applications of the new crystal form. According to the invention, the prepared new crystal form for preparing lorazepam shows excellent properties defined in the specification.

Light-stabilized pharmaceutical composition, and preparation method and pharmaceutical application thereof

The invention relates to a light-stabilized pharmaceutical composition, and a preparation method and pharmaceutical application thereof. Specifically, the pharmaceutical composition comprises a lorazepam crystal and pharmaceutical adjuvants. The lorazepam crystal is radiated by Cu-K alpha. In a powder X-ray diffraction pattern expressed by an angle of 2 theta, there are diffraction peaks at approximately 12.17 degrees, approximately 14.15 degrees, approximately 15.27 degrees, approximately 16.84 degrees, approximately 17.91 degrees and approximately 20.81 degrees. For example, the crystal hasdiffraction peaks at approximately 7.93 degrees, approximately 9.04 degrees, approximately 12.17 degrees, approximately 14.15 degrees, approximately 15.27 degrees, approximately 16.84 degrees, approximately 17.91 degrees, approximately 20.81 degrees, approximately 21.44 degrees and approximately 26.38 degrees. A new crystal form and the pharmaceutical composition, which are used for preparing lorazepam and prepared by the method, exhibit excellent properties as described in the description of the invention.

Method for preparing lorazepam

The invention relates to a method for preparing lorazepam. The method comprises the following steps: subjecting a ketone substrate as shown in a formula I, glacial acetic acid, potassium acetate, potassium persulfate and iodine to a reaction under heating and stirring conditions to obtain an acetoxy substrate as shown in a formula II; dropwise adding a sodium hydroxide solution into a mixture of ethanol and the acetoxy substance as shown in the formula II, carrying out stirring to realize a complete reaction, performing filtering to obtain a filter cake, and reacting the filter cake with ethylacetate and a citric acid solution to obtain a crude lorazepam product; and crystallizing the crude lorazepam product by using ethanol and ethyl acetate in sequence. The invention further relates tothe pharmaceutical application of larazepam prepared by using the method. The larazepam is particularly used for treating or preventing anxiety, epilepsy, convulsion, sedation and hypnosis. The methoddisclosed by the invention has excellent technical effects as described in the specification.

Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase

A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.

Enantioselective potential of polysaccharide-based chiral stationary phases in supercritical fluid chromatography

The enantioselective potential of two polysaccharide-based chiral stationary phases for analysis of chiral structurally diverse biologically active compounds was evaluated in supercritical fluid chromatography using a set of 52 analytes. The chiral selectors immobilized on 2.5?μm silica particles were tris-(3,5-dimethylphenylcarmabate) derivatives of cellulose or amylose. The influence of the polysaccharide backbone, different organic modifiers, and different mobile phase additives on retention and enantioseparation was monitored. Conditions for fast baseline enantioseparation were found for the majority of the compounds. The success rate of baseline and partial enantioseparation with cellulose-based chiral stationary phase was 51.9% and 15.4%, respectively. Using amylose-based chiral stationary phase we obtained 76.9% of baseline enantioseparations and 9.6% of partial enantioseparations of the tested compounds. The best results on cellulose-based chiral stationary phase were achieved particularly with propane-2-ol and a mixture of isopropylamine and trifluoroacetic acid as organic modifier and additive to CO2, respectively. Methanol and basic additive isopropylamine were preferred on amylose-based chiral stationary phase. The complementary enantioselectivity of the cellulose- and amylose-based chiral stationary phases allows separation of the majority of the tested structurally different compounds. Separation systems were found to be directly applicable for analyses of biologically active compounds of interest.

Development of new HPLC chiral stationary phases based on native and derivatized cyclofructans

An unusual class of chiral selectors, cyclofructans, is introduced for the first time as bonded chiral stationary phases. Compared to native cyclofructans (CFs), which have rather limited capabilities as chiral selectors, aliphatic-and aromatic-functionalized CF6s possess unique and very different enantiomeric selectivities. Indeed, they are shown to separate a very broad range of racemic compounds. In particular, aliphatic-derivatized CF6s with a low substitution degree baseline separate all tested chiral primary amines. It appears that partial derivatization on the CF6 molecule disrupts the molecular internal hydrogen bonding, thereby making the core of the molecule more accessible. In contrast, highly aromaticfunctionalized CF6 stationary phases lose most of the enantioselective capabilities toward primary amines, however they gain broad selectivity for most other types of analytes. This class of stationary phases also demonstrates high "loadability" and therefore has great potential for preparative separations. The variations in enantiomeric selectivity often can be correlated with distinct structural features of the selector. The separations occur predominantly in the presence of organic solvents.

Efficient synthesis of 3-hydroxy-1,4-benzodiazepines oxazepam and lorazepam by new acetoxylation reaction of 3-position of 1,4-benzodiazepine ring

Simple, efficient, and scalable syntheses of 3-hydroxy-1,4-benzodiazepines, oxazepam (1), and lorazepam (2) were developed. The syntheses are based on the new acetoxylation reaction of the 3-position of the 1,4-benzodiazepine ring. The reaction involves iodine (20-50 mol %)-catalyzed acetoxylation in the presence of potassium acetate (2 equiv) and potassium peroxydisulfate (1-2 equiv) as a stoichiontetric oxidant affording the corresponding 3-acetoxy-1,4- benzodiazepines in good-to-high yields. The latter were converted by selective saponification to 3-hydroxy-1,4-benzodiazepines of very high purity (>99.8%) in an overall yield of 83% (oxazepam) and 64% (lorazepam).

A METHOD OF PURIFICATION OF LORAZEPAM

A new method of purification of Lorazepam is disclosed that consists in removing products of synthesis, decomposition products, water or other solvent that forms a solvate with Lorazepam, by crystallization or stirring in an organic solvent of the ether, ester or ketone type. Lorazepam prepared via this method can be utilized in the pharmaceutical industry for the manufacture of pharmaceuticals.

Process for preparing pure crystalline lorazepam

The present invention provides a process for preparing crystalline lorazepam substantially free of bound solvent from a lorazepam alcohol solvate or hydrate by suspending the lorazepam solvate in an organic medium selected from ethyl acetate, cyclohexane, dichloromethane, toluene and mixtures thereof. This process is useful in producing the anti-anxiety and sedative agent lorazepam in increased yields. A process for converting lorazepam lower alcohol solvates to lorazepam hydrate is also disclosed.

Process for preparing pure crystalline lorazepam

The present invention provides a process for preparing crystalline lorazepam substantially free of bound solvent from a lorazepam alcohol solvate or hydrate by suspending the lorazepam solvate in an organic medium selected from ethyl acetate, cyclohexane, dichloromethane, toluene and mixtures thereof. This process is useful in producing the anti-anxiety and sedative agent lorazepam in increased yields. A process for converting lorazepam lower alcohol solvates to lorazepam hydrate is also disclosed.