127785-96-0

Usage

Uses

Used in Pharmaceutical Industry:
6-Aminomethyl-6,11-dihydro-5H-dibenz[b,e]azepine (E)-2-butenedioate is used as an antipsychotic agent for the treatment of schizophrenia and related disorders. It is particularly effective in managing the symptoms of the condition, such as hallucinations, delusions, and disorganized thinking.
Used in Mental Health Care:
6-Aminomethyl-6,11-dihydro-5H-dibenz[b,e]azepine (E)-2-butenedioate is used as a medication to reduce the risk of suicidal behavior in individuals with schizophrenia or similar mental health disorders, providing an essential intervention for those at high risk.
However, due to its association with potentially serious side effects, including agranulocytosis—a severe decrease in white blood cells—along with seizures, myocarditis, and other adverse reactions, clozapine is typically reserved for patients who have not responded to other antipsychotic medications. This cautious approach ensures that its use is balanced with the potential risks it may pose to patients.

InChI:InChI=1/C15H16N2.C4H4O4/c16-10-15-13-7-3-1-5-11(13)9-12-6-2-4-8-14(12)17-15;5-3(6)1-2-4(7)8/h1-8,15,17H,9-10,16H2;1-2H,(H,5,6)(H,7,8)/b;2-1+

Synthetic route

N-<(11H-dibenzazepin-6-yl)methyl>phthalimide (74860-00-7) + (2E)-but-2-enedioic acid (110-17-8) → 6,11-dihydro-5H-dibenzazepine-6-methanamine fumarate (127785-96-0)

Conditions	Yield
Stage #1: N-<(11H-dibenzazepin-6-yl)methyl>phthalimide With sodium tetrahydroborate In methanol; water; isopropyl alcohol; toluene at 20 - 30℃; for 24.5h; Stage #2: With hydrogenchloride In water; isopropyl alcohol at 20 - 80℃; for 1.5h; Stage #3: (2E)-but-2-enedioic acid With sodium hydroxide Product distribution / selectivity; more than 3 stages;	76.1%
Stage #1: N-<(11H-dibenzazepin-6-yl)methyl>phthalimide With sodium tetrahydroborate In methanol; water; isopropyl alcohol; toluene at 20 - 30℃; for 24.5h; Stage #2: With methanol; sodium hydroxide In water; isopropyl alcohol at 20 - 80℃; for 1.5h; Stage #3: (2E)-but-2-enedioic acid In methanol at 0 - 20℃; for 3h; Product distribution / selectivity;	72.4%
Stage #1: N-<(11H-dibenzazepin-6-yl)methyl>phthalimide With sodium tetrahydroborate In water; isopropyl alcohol at 20 - 30℃; for 24.5h; Stage #2: With acetic acid In water; isopropyl alcohol at 20 - 80℃; for 1.5h; Stage #3: (2E)-but-2-enedioic acid With sodium hydroxide Product distribution / selectivity; more than 3 stages;	69%

6-aminomethyl-6,11-dihydro-5H-dibenzo[b,e]azepine (41218-84-2) + (2E)-but-2-enedioic acid (110-17-8) → 6,11-dihydro-5H-dibenzazepine-6-methanamine fumarate (127785-96-0)

Conditions	Yield
In methanol at 20℃; for 1h;	76%
In methanol at 35 - 40℃; for 1.5 - 1.66667h;

N-[2-(phenylmethyl)phenyl]-2-chloroacetamide (21535-43-3) → 6,11-dihydro-5H-dibenzazepine-6-methanamine fumarate (127785-96-0)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: trichlorophosphate / toluene / 6 h / 65 - 90 °C 2.1: potassium hydroxide / N,N-dimethyl-formamide / 55 °C 2.2: 15 h / 45 °C 3.1: formic acid; hydrogen; 5%-palladium/activated carbon / N,N-dimethyl-formamide / 24 h / 70 °C / 7500.75 Torr 4.1: hydrogenchloride / glycerol; water / 2.5 h / 20 - 110 °C 5.1: methanol / 1 h / 20 °C View Scheme

6-(chloromethyl)-11H-dibenzazepine (21535-44-4) → 6,11-dihydro-5H-dibenzazepine-6-methanamine fumarate (127785-96-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium hydroxide / N,N-dimethyl-formamide / 55 °C 1.2: 15 h / 45 °C 2.1: formic acid; hydrogen; 5%-palladium/activated carbon / N,N-dimethyl-formamide / 24 h / 70 °C / 7500.75 Torr 3.1: hydrogenchloride / glycerol; water / 2.5 h / 20 - 110 °C 4.1: methanol / 1 h / 20 °C View Scheme

6-cyclopropylaminomethyl-5H-dibenz(b,e)azepine → 6,11-dihydro-5H-dibenzazepine-6-methanamine fumarate (127785-96-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: formic acid; hydrogen; 5%-palladium/activated carbon / N,N-dimethyl-formamide / 24 h / 70 °C / 7500.75 Torr 2: hydrogenchloride / glycerol; water / 2.5 h / 20 - 110 °C 3: methanol / 1 h / 20 °C View Scheme

6-cyclopropylaminomethyl-6,11-dihydro-5H-dibenz(b,e)azepine → 6,11-dihydro-5H-dibenzazepine-6-methanamine fumarate (127785-96-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / glycerol; water / 2.5 h / 20 - 110 °C 2: methanol / 1 h / 20 °C View Scheme

6,11-dihydro-5H-dibenzazepine-6-methanamine fumarate (127785-96-0) + O-methyl-N-(methoxycarbonyl)-isourea (40943-37-1) → {imino[N-(5H-dibenz[b,e]azepin-6-yl)methylamino]methyl}carbamate

Conditions	Yield
In dimethyl sulfoxide at 40℃; for 22h; Solvent;	94%

6,11-dihydro-5H-dibenzazepine-6-methanamine fumarate (127785-96-0) → epinastine (80012-43-7)

Conditions	Yield
With sodium hydroxide In water at 25 - 30℃; for 0.5h;

N-(iminomethoxymethyl)allylcarbamate + 6,11-dihydro-5H-dibenzazepine-6-methanamine fumarate (127785-96-0) → {imino[N-(5H-dibenz[b,e]azepin-6-yl)methylamino]allyl}carbamate

Conditions	Yield
In N,N-dimethyl-formamide at 50℃; for 21h;

6,11-dihydro-5H-dibenzazepine-6-methanamine fumarate (127785-96-0) → 3-amino-9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepine hydrochloride

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethyl sulfoxide / 22 h / 40 °C 2: acetic acid / toluene / 23 h / 90 °C View Scheme

Upstream product

• 41218-84-2 6-aminomethyl-6,11-dihydro-5H-dibenzo[b,e]azepine 
• 110-17-8 (2E)-but-2-enedioic acid 
• 74860-00-7 N-<(11H-dibenzazepin-6-yl)methyl>phthalimide 
• 21535-43-3 N-[2-(phenylmethyl)phenyl]-2-chloroacetamide 
• 21535-44-4 6-(chloromethyl)-11H-dibenzazepine 

Downstream Products

• 80012-43-7 epinastine 

Relevant academic research and scientific papers

A new process for the preparation of 3-amino-9,13b-dihydro-1H-dibenz [c,f] imidazo[1,5-a]azepine bromic acid salt

The present invention relates to a novel method for preparing an enhanced 3-amino-9, 13b-dihydro-1H-dibenz [c,f] imidazo [1,5-a] azepine bromic acid salt. The compound is used as an intermediate in manufacturing the epinastine hydrochloride. The compound is represented by the structural formula (I).COPYRIGHT KIPO 2015

NOVEL CRYSTAL MODIFICATION OF EPINASTINE OR SALTS THEREOF AND PROCESS FOR PREPARATION THEREOF

The present invention provides novel crystalline forms of 3-amino-9,13b-dihydro-lH- dibenzo[c,f]imidazo[l55-a] azepine or salts thereof and process for preparation thereof.

METHOD FOR PREPARING 6-AMINOMETHYL-6,11-DIHYDRO-5H-DIBENZ(B,E)AZEPINE

A production method of 6-aminomethyl-6,11-dihydro-5H-dibenz[b,e]azepin characterized in that said compound is produced via N-[(6,11-dihydro-5H-dibenz[b,e]azepin-6-yl)methyl]-o-hydroxymethylbenzamide which is prepared by reducing 2-(11H-dibenz[b,e]azepin-6-ylmethyl)-1H-isoindole-1,3(2H)-dione employing a metal hydride or a metal hydride complex in a water based alcohol, and N-[(6,11-dihydro-5H-dibenz[b,e]azepin-6-yl)methyl]-o-hydroxymethylbenzamide which is useful for the aforesaid production method.