2647-50-9

Basic information

• Product Name: Flubromazepam
• Synonyms: 7-broMo-5-(2-fluorophenyl)-1H-benzo[e][1,4]diazepin-2(3H)-one;FlubroMazepaM;7-Bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one;7-Bromo-5-(2-fluorophenyl)-1,3-dihydrobenzo[e]-1,4-diazepin-2-one;2H-1,4-Benzodiazepin-2-one, 7-broMo-5-(2-fluorophenyl)-1,3-dihydro-;7-bromo-5-(2-fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS NO: 2647-50-9
• Molecular Formula: C₁₅H₁₀BrFN₂O
• Molecular Weight: 333.1551032
• Product Categories: research chemical;chemical research;pharmaceutical intermdeiate;medicine grade
• Mol File: 2647-50-9.mol
• Article Data: 7

Chemical Properties

• Melting Point: 189-190℃
• Boiling Point: 465.7±45.0 °C(Predicted)
• Appearance: /
• Density: 1.58±0.1 g/cm3(Predicted)
• PKA: 11.55±0.70(Predicted)
• CAS DataBase Reference: Flubromazepam(CAS DataBase Reference)
• NIST Chemistry Reference: Flubromazepam(2647-50-9)
• EPA Substance Registry System: Flubromazepam(2647-50-9)

Safety Data

• Hazardous Substances Data: 2647-50-9(Hazardous Substances Data)

Usage

Description

Flubromazepam is a potent, long-acting designer benzodiazepine drug that is structurally related to Phenazepam. It possesses anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. Flubromazepam is categorized as an analytical reference standard and has been detected in seized samples. It is known for its anxiolytic and sedative properties, and it is used in research and forensic applications. However, it also has a high addiction potential and risk of overdose.

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 
• 2824-08-0 N⁽¹⁾-[4-bromo-2-[(2-fluorophenyl)carbonyl]phenyl]glycinamide 
• 304854-54-4 2-amino-5-bromo-N-methoxy-N-methyl-benzamide 
• 87-48-9 5-Bromo-1H-indole-2,3-dione 
• 74189-16-5 2-amino-5-bromobenzoic acid hydrochloride 

Downstream Products

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

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