127785-96-0

Basic information

• Product Name: 6-Aminomethyl-6,11-dihydro-5H-dibenz[b,e]azepine (E)-2-butenedioate
• Synonyms: 6-AMIOMETHYL-6,11-DIHYDRO-5H-DIBENZ[B,E]AZEPIN(E)-2-BUTANEDIOATE(1:1);6-AMINOMETHYL-6,11-DIHYDRO-5H-DIBENZ[B,E]AZEPINE (E)-2-BUTENEDIOATE;(6,11-Dihydro-5H-dibenzo[b,e]azepin-6-yl)MethanaMine fuMarate;6-aMinoMethyl-6,11-dihydro-5H-dibenz[b,e]azepine succinate;6-AMINOMETHYL-6, 11-DIHYDRO-5H-DIBENEZ[B,E]AZEPINE (E)-2-BUTENEDIOATE
• CAS NO: 127785-96-0
• Molecular Formula: C₄H₄O₄*C₁₅H₁₆N₂
• Molecular Weight: 340.37
• EINECS: 1312995-182-4
• Mol File: 127785-96-0.mol
• Article Data: 3

Chemical Properties

• Melting Point: 194-195 °C (decomp)
• Boiling Point: 616.9 °C at 760 mmHg
• Flash Point: Flash Point: 326.9 °C
• Appearance: /
• Vapor Pressure: 4.48E-16mmHg at 25°C
• Storage Temp.: Inert atmosphere,Room Temperature
• CAS DataBase Reference: 6-Aminomethyl-6,11-dihydro-5H-dibenz[b,e]azepine (E)-2-butenedioate(CAS DataBase Reference)
• NIST Chemistry Reference: 6-Aminomethyl-6,11-dihydro-5H-dibenz[b,e]azepine (E)-2-butenedioate(127785-96-0)
• EPA Substance Registry System: 6-Aminomethyl-6,11-dihydro-5H-dibenz[b,e]azepine (E)-2-butenedioate(127785-96-0)

Safety Data

• Hazardous Substances Data: 127785-96-0(Hazardous Substances Data)

Usage

General Description

6-Aminomethyl-6,11-dihydro-5H-dibenz[b,e]azepine (E)-2-butenedioate is a chemical compound that is also known as clozapine. It is an antipsychotic medication that is used to treat schizophrenia, as well as reducing the risk of suicidal behavior in people with schizophrenia or similar disorders. Clozapine works by affecting the balance of chemicals in the brain, specifically by blocking the receptors for dopamine and serotonin. It is typically taken orally and has been shown to be effective in treating the symptoms of schizophrenia, such as hallucinations, delusions, and disorganized thinking. However, it is associated with potentially serious side effects, including a risk of agranulocytosis, which is a severe decrease in white blood cells, as well as seizures, myocarditis, and other adverse reactions. Therefore, it is generally reserved for patients who have not responded to other antipsychotic medications.

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

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

Downstream Products

• 80012-43-7 epinastine 

Relevant articles and documents

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

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.