2647-50-9

Usage

Uses

Used in Pharmaceutical Industry:
Flubromazepam is used as a treatment for neurological disorders such as epilepsy, alcohol withdrawal, and insomnia. It helps alleviate symptoms and improve the quality of life for patients suffering from these conditions.
Used in Preoperative Medication:
Flubromazepam is used as a premedication before surgery due to its ability to augment the effects of anesthetics and reduce anxiety in patients. This helps ensure a smoother and more comfortable surgical experience.
Used in Forensic Analysis:
Flubromazepam is used as a starting material in calibrators and controls for various gas chromatography/mass spectrometry (GC/MS) or liquid chromatography/mass spectrometry (LC/MS) applications. This aids in the detection and analysis of the drug in forensic cases, clinical toxicology, and urine drug testing.
Used in Research and Development:
Flubromazepam serves as an important research compound for the development of new drugs and therapies related to its anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. It helps scientists understand the mechanisms of action and potential applications in various medical conditions.

Synthetic route

5-bromo-2-bromoacetamido-2'-fluorobenzophenone (1647-74-1) → 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9)

Conditions	Yield
With ammonia In methanol for 16h; Heating / reflux;	56.8%
With ammonia for 5h; Heating;	4.5 g
With ammonia In methanol for 18h;	98.6 mg
With ammonia In methanol at 0 - 20℃;	68 mg

5-bromo-2'-fluoro-2-aminobenzophenone (1479-58-9) + 2-Bromoacetyl bromide (598-21-0) → 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9)

Conditions	Yield
Stage #1: 5-bromo-2'-fluoro-2-aminobenzophenone; 2-Bromoacetyl bromide With sodium hydrogencarbonate In dichloromethane Stage #2: With ammonia In methanol Heating / reflux;
Stage #1: 5-bromo-2'-fluoro-2-aminobenzophenone; 2-Bromoacetyl bromide With sodium hydrogencarbonate In dichloromethane Stage #2: With ammonia In methanol Heating / reflux;

N(1)-[4-bromo-2-[(2-fluorophenyl)carbonyl]phenyl]glycinamide (2824-08-0) → 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9)

Conditions	Yield
With acetic acid In ethanol for 0.25h; Heating / reflux;

2-amino-5-bromo-N-methoxy-N-methyl-benzamide (304854-54-4) → 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -100 °C / Inert atmosphere 2: tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 3: ammonia / methanol / 18 h View Scheme

5-bromo-2'-fluoro-2-aminobenzophenone (1479-58-9) → 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 2: ammonia / methanol / 18 h View Scheme
Multi-step reaction with 2 steps 1: sodium carbonate / dichloromethane; water / 2 h / 0 °C 2: ammonia / methanol / 0 - 20 °C View Scheme

5-Bromo-1H-indole-2,3-dione (87-48-9) → 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: sodium hydroxide; dihydrogen peroxide / water / 0.5 h / 50 °C 1.2: pH Ca. 4 2.1: 4-methyl-morpholine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 3.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -100 °C / Inert atmosphere 4.1: tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 5.1: ammonia / methanol / 18 h View Scheme

2-amino-5-bromobenzoic acid hydrochloride (74189-16-5) → 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 4-methyl-morpholine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 2: n-butyllithium / tetrahydrofuran; hexane / 1 h / -100 °C / Inert atmosphere 3: tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 4: ammonia / methanol / 18 h View Scheme

7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9) → 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one 4-oxide (10329-38-1)

Conditions	Yield
With peracetic acid In dichloromethane for 4.5h; Ambient temperature;	80.9%

propionaldehyde (123-38-6) + 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9) → 7-bromo-5-(2-fluorophenyl)-4-propyl-1,3,4,5-tetrahydro-2H-benzo[e][1,4]diazepin-2-one

Conditions	Yield
Stage #1: 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one With sodium cyanoborohydride; acetic acid In methanol at 20℃; for 4h; Stage #2: propionaldehyde In methanol at 20℃;	62%

Ethyl isocyanoacetate (2999-46-4) + 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9) → ethyl 8-bromo-6-(2'-fluorophenyl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate (612526-24-6)

Conditions	Yield
Stage #1: 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: With diethyl chlorophosphate In tetrahydrofuran at 0℃; for 0.5h; Stage #3: Ethyl isocyanoacetate In tetrahydrofuran at 0℃; for 1h;	58%
Stage #1: 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one With sodium hydride In tetrahydrofuran at 0℃; for 0.333333h; Stage #2: With diethyl chlorophosphate In tetrahydrofuran at 0℃; for 0.5h; Stage #3: Ethyl isocyanoacetate With sodium hydride; acetic acid more than 3 stages;

7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9) + trimethylsilylacetylene (1066-54-2) → 5-(2-fluoro-phenyl)-7-trimethylsilylacetyleno-1,3-dihydro-benzo[e][1,4]diazepin-2-one

Conditions	Yield
With triethylamine; bis(triphenylphosphine) palladium (Il) acetate In acetonitrile for 3h; Heating / reflux;	47%
With triethylamine In acetonitrile for 3h; Heck Reaction; Heating / reflux;	47%

acetic acid hydrazide (1068-57-1) + 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9) → flubromazolam (612526-40-6)

Conditions	Yield
Stage #1: 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one With sodium hydride In tetrahydrofuran at 0℃; for 1h; Stage #2: With di-morpholin-4-yl-phosphinic acid chloride In tetrahydrofuran at 0 - 20℃; for 2h; Stage #3: acetic acid hydrazide In tetrahydrofuran; butan-1-ol at 20℃; for 2.25h; Heating / reflux;	40%

7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9) → Acetic acid 7-bromo-5-(2-fluoro-phenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 80.9 percent / 40percent peroxyacetic acid / CH2Cl2 / 4.5 h / Ambient temperature 2: 6.5 g / 3 h / 0 °C View Scheme

7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9) → 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (62659-65-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 80.9 percent / 40percent peroxyacetic acid / CH2Cl2 / 4.5 h / Ambient temperature 2: 6.5 g / 3 h / 0 °C 3: 3.3 g / 1 N NaOH / methanol / 0.5 h / 25 °C View Scheme

7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (2647-50-9) → 7-bromo-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine (885124-07-2)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 20℃;

Upstream product

• 1647-74-1 5-bromo-2-bromoacetamido-2'-fluorobenzophenone 
• 1479-58-9 5-bromo-2'-fluoro-2-aminobenzophenone 
• 598-21-0 2-Bromoacetyl bromide 
• 304854-54-4 2-amino-5-bromo-N-methoxy-N-methyl-benzamide 
• 74189-16-5 2-amino-5-bromobenzoic acid hydrochloride 
• 87-48-9 5-Bromo-1H-indole-2,3-dione 
• 2824-08-0 N⁽¹⁾-[4-bromo-2-[(2-fluorophenyl)carbonyl]phenyl]glycinamide 

Downstream Products

• 612526-40-6 flubromazolam 
• 612526-24-6 ethyl 8-bromo-6-(2'-fluorophenyl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate 
• 885124-07-2 7-bromo-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine 
• 62659-65-8 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one 
• 10329-38-1 7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one 4-oxide 

Relevant academic research and scientific papers

Structure-Activity Relationship Studies of Retro-1 Analogues against Shiga Toxin

High-throughput screening has shown that Retro-1 inhibits ricin and Shiga toxins by diminishing their intracellular trafficking via the retrograde route, from early endosomes to the Golgi apparatus. To improve the activity of Retro-1, a structure-activity relationship (SAR) study was undertaken and yielded an analogue with a roughly 70-fold better half-maximal effective concentration (EC50) against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.

Synthesis of Flubromazepam Positional Isomers for Forensic Analysis

Designer benzodiazepines have recently appeared in many forensic cases as legal alternatives to federally scheduled drugs such as diazepam (Valium) and alprazolam (Xanax). Though current forensic instrumental techniques are often sufficient for identifying novel psychoactive substances, they may not readily differentiate between potential positional isomers. Additionally, characterization data for positional isomers of known designer benzodiazepines are widely nonexistent. In this study, flubromazepam, a recognized designer benzodiazepine since 2012, was targeted for synthesis and characterization due to its potential for federal scheduling and current legal status within the United States. A practical synthetic method was developed to prepare purified reference materials for each positional isomer of flubromazepam in which the positions of the bromine and fluorine substituents were varied. Possible isomers (9 of the 12) were successfully prepared and used for further analysis.

Carboxamide GABAa ALPHA2 Modulators

The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating CNS disorders.

Stereospecific anxiolytic and anticonvulsant agents with reduced muscle-relaxant, sedative-hypnotic and ataxic effects

The present invention provides compositions and methods of using stereospecific benzodiazepine derivatives, their salts and prodrugs for the treatment of anxiolytic or convulsant disorders having the side effects of reduced alcohol craving in human alcoholics and a concomitant reduced sedative, hypnotic, muscle relaxant and ataxic side-effects. The invention further provides pharmaceutical compositions for treatment of anxiolytic and convulsant disorders in subjects in need thereof, comprising a compound, prodrug or a salt having a chemical structure represented by any one of Formula I-XXI and a pharmaceutically-acceptable carrier.

CHEMICAL COMPOUNDS

The present invention relates to dihydrobenzodiazepine derivatives, compositions and medicaments containing the same, as well as processes for the preparation and use of such compounds, compositions and medicaments. Such dihydrobenzodiazepine derivatives

ANXIOLYTIC AGENTS WITH REDUCED SEDATIVE AND ATAXIC EFFECTS

Orally active benzodiazepine derivatives and their salts are disclosed. These compounds and their salts have anxiolytic and anticonvulsant activity with reduced sedative/hypnotic/muscle relaxant/ataxic effects.

Asymmetric Transformation. II. Racemization Reaction of 1,4-Benzodiazepinooxazole Derivative

Optically active crystals of 10-bromo-11b-(2-fluorophenyl)-2,3,7,11b-tetrahydrooxazolo-benzodiazepin-6(5H)-one were obtained by preferential crystallization; they were sometimes levorotatory and sometimes dextrorotatory.This phenomenon was pro