846-49-1

Basic information

• Product Name: Lorazepam
• Synonyms: (±)-Lorazepam solution;8133 CB;7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one;7-Chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepine-2-one;Lorazepam CIV (200 mg)I1D4040.998mg/mg(ai);Lorazepam CIV (200 mg);Acetonitrile( Test Lorazepam, 1.0 mg/mL );LorazepaM (CIV), USP
• CAS NO: 846-49-1
• Molecular Formula: C₁₅H₁₀Cl₂N₂O₂
• Molecular Weight: 321.16
• EINECS: 212-687-6
• Product Categories: API's;Intermediates & Fine Chemicals;Pharmaceuticals;Isotope Labeled Compounds;Lorazepam ada@tuskwei.com whatsapp;8618031153937
• Mol File: 846-49-1.mol
• Article Data: 10

Chemical Properties

• Melting Point: 166-168°C
• Boiling Point: 533.8 °C at 760 mmHg
• Flash Point: 11 °C
• Appearance: White crystalline solid
• Density: 1.4835 (rough estimate)
• Refractive Index: 1.6070 (estimate)
• Storage Temp.: −20°C
• Solubility: Practically insoluble in water, sparingly soluble in ethanol (96 per cent), sparingly soluble or slightly soluble in methylene chloride.
• PKA: pK1 1.3; pK2 11.5(at 25℃)
• Water Solubility: 54mg/L(temperature not stated)
• Stability: hygroscopic
• CAS DataBase Reference: Lorazepam(CAS DataBase Reference)
• NIST Chemistry Reference: Lorazepam(846-49-1)
• EPA Substance Registry System: Lorazepam(846-49-1)

Safety Data

• Hazard Codes: Xn,T,F
• Statements: 63-39/23/24/25-23/24/25-11-36-20/21/22
• Safety Statements: 36/37-45-16
• RIDADR: UN 1230 3/PG 2
• WGK Germany: 3
• RTECS: DF0350000
• Hazardous Substances Data: 846-49-1(Hazardous Substances Data)

Usage

Chemical Properties

White Crystalline Solid

Originator

Tavor,Wyeth,Italy,1972

Uses

An anxiolytic, and anticonvulsant. Controlled substance (depressant)

Manufacturing Process

The starting material was 2-amino-2',5-dichlorobenzophenone which was reacted with hydroxylamine and then with chloroacetyl chloride. The intermediate thus obtained is reacted with methylamine and then with acetic anhydride. To a slightly warm suspension of 3-acetoxy-7-chloro-5-(o-chlorophenyl)-1,3- dihydro-2H-1,4-benzodiazepin-2-one thus obtained was added 4N sodium hydroxide solution with stirring. All the solid dissolved and soon a thick white solid precipitated out. The solid was filtered, washed well with water and recrystallized from ethanol. The product was isolated as a solvate with 1 mol of ethanol. When heated it loses the ethanol of solvation and melts at 166°C to 168°C.

Brand name

Ativan (Baxter Healthcare); Ativan (Biovail); Loraz (Quantum Pharmics).

Therapeutic Function

Tranquilizer

General Description

Lorazepam, 7-chloro-5-(2-chlorophenyl)-3-dihydro-3-hydroxy-2H-1,4-benzodiazepine-2-one(Ativan), is the 2'-chloro derivative of oxazepam. In keepingwith overall SARs, the 2'-chloro substituent increases activity.As with oxazepam, metabolism is relatively rapid anduncomplicated because of the 3-hydroxyl group in the compound.Thus, it also has short half-life (2–6 hours) and similarpharmacological activity.

InChI:InChI=1/C15H10Cl2N2O2/c16-8-5-6-12-10(7-8)13(19-15(21)14(20)18-12)9-3-1-2-4-11(9)17/h1-7,15,21H,(H,18,20)

Upstream product

• 848-75-9 lormetazepam 
• 2848-96-6 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2-oxo-2H-1,4-benzodiazepin-3-yl acetate 
• 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 
• 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 
• 130753-89-8 7-chloro-5-(2-chlorophenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl 2-(6-methoxynaphthalen-2-yl)propanoate 
• 82841-78-9 lorazepam-α-chloro-propionate 
• 71107-65-8 lorazepam-β-phenyl-propionate 
• 71107-66-9 lorazepam-α-methyl-β-phenyl-propionate 
• 2958-36-3 (2-amino-5-chloro-phenyl)-(2-chloro-phenyl)-methanone 
• 60628-61-7 7-chloro-5-(2-chloro-phenyl)-3-fluoro-1,3-dihydro-benzo[e][1,4]diazepin-2-one 
• 128493-74-3 (C₆H₃Cl)NCOCH(OH)NC(C₆H₄Cl)AuP(C₆H₅)3 
• 82384-75-6 (7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one)AuCl₃ 
• 848-75-9 lormetazepam 

Relevant articles and documents

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.

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.

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.