111974-74-4

Basic information

• Product Name: 11-(1-Piperazinyl)-dibenzo[b,f][1,4]thiazepine dihydrochloride
• Synonyms: Quetiapine Related CoMpound B;11-piperazinyl-dibenzo d,f 1,4 thiazepine dihydrochloride;N-Des[2-(2-hydroxyethoxy)ethyl] Quetiapine Dihydrochloride (1.0 Mg/ML in Methanol);Quetiapine Impurity B DiHCl;Quetiapine EP Impurity B;Dibenzo[b,f][1,4] thiazepine-11-amine Hydrochloride;11-(1-piperazinyl)-dibenzo[b,f][1,4]thiazepine dihydrochloride;11-Piperazinodibenzo[b,f][1,4]thiazepine dihydrochloride
• CAS NO: 111974-74-4
• Molecular Formula: C17H19Cl2N3S
• Molecular Weight: 368.32386
• EINECS: 1312995-182-4
• Product Categories: (intermediate of quetiapine fumarate);Heterocyclic Compounds;Heterocycles;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Quetiapine
• Mol File: 111974-74-4.mol
• Article Data: 12

Chemical Properties

• Melting Point: 180-184°C
• Boiling Point: 513.3 °C at 760 mmHg
• Flash Point: 264.3 °C
• Appearance: pale-yellow solid
• Vapor Pressure: 6.63E-11mmHg at 25°C
• Storage Temp.: -20°C Freezer
• Solubility: Soluble in DMSO, Methanol, Distilled Water
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO, methanol, or distilled water may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: 11-(1-Piperazinyl)-dibenzo[b,f][1,4]thiazepine dihydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 11-(1-Piperazinyl)-dibenzo[b,f][1,4]thiazepine dihydrochloride(111974-74-4)
• EPA Substance Registry System: 11-(1-Piperazinyl)-dibenzo[b,f][1,4]thiazepine dihydrochloride(111974-74-4)

Safety Data

• Hazardous Substances Data: 111974-74-4(Hazardous Substances Data)

Usage

Description

Norquetiapine 2HCl (111974-74-4) is a pharmacologically active metabolite of quetiapine (Seroquel).1? Exhibits distinct pharmacological activity from quetiapine and plays an important role in its antidepressant activity.2? Activates ERK1/2 and induces release of BDNF in C6 glioma cells which may contribute to the antidepressant properties of quetiapine.3?Inhibits the norepinephrine transporter which may contribute to the antipsychotic activity of quetiapine.4

Chemical Properties

11-(1-Piperazinyl)-dibenzo[b,f][1,4]thiazepine dihydrochloride is Pale-Yellow Solid

Uses

Different sources of media describe the Uses of 111974-74-4 differently. You can refer to the following data:
1. 11-(1-Piperazinyl)-dibenzo[b,f][1,4]thiazepine dihydrochloride is a metabolite of Quetiapine, a Benzothiazepine with mixed serotonin and dopamine receptor antagonistic properties used as an antipsychotic
2. N-Des[2-(2-hydroxyethoxy)ethyl] Quetiapine Dihydrochloride (Quetiapine EP Impurity B) is a metabolite of Quetiapine, a Benzothiazepine with mixed serotonin and dopamine receptor antagonistic properties used as an antipsychotic.

References

1) Altamura?et al.?(2012),?Effect of quetiapine and norquetiapine on anxiety and depression in major psychoses using a pharmacokinetic approach: a prospective observational study; Clin. Drug Investig.,?32?213 2) Lopez Munoz and Alamo (2013),?Active metabolites as antidepressant drugs: the role of norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders; Front. Psychiatry,?4?102 3) Di. Benedetto?et al.?(2012),?N-desalkylquetiapine activates ERK1/2 to induce GDNF release in C6 glioma cells: a putative cellular mechanism for quetiapine as antidepressant; Neuropharmacology,?62?209 4) Bjorkholm?et al.?(2013),?Role of concomitant inhibition of the norepinephrine transporter for the antipsychotic effect of quetiapine; Eur. Neuropsychopharmacol.,?23?709

InChI:InChI=1/C17H17N3S.2ClH/c1-3-7-15-13(5-1)17(20-11-9-18-10-12-20)19-14-6-2-4-8-16(14)21-15;;/h1-8,18H,9-12H2;2*1H

Upstream product

• 5747-48-8 11-(1-piperazinyl)dibenzo[b,f][1,4]thiazepine 
• 13745-86-3 11-chloro-dibenzo[b,f][1,4]thiazepine 
• 3159-07-7 dibenzo[b,f][1,4]thiazepin-11-one 
• 110-85-0 piperazine 
• 114724-41-3 2-(2-aminophenylthio)benzoic acid hydrochloride 
• 88-73-3 2-Chloronitrobenzene 
• 7647-01-0 hydrogenchloride 

Relevant articles and documents

Design, synthesis and anticancer activity of N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives

Novel N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives were designed, synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR and Mass spectra. The anticancer activities of the newly synthesized compounds were evaluated in vitro against three human cancer cell lines including K562, Colo-205 and MDA-MB 231 by MTT assay. The screening results showed that five compounds (16b, 16d, 16i, 16p and 16q) exhibited potent cytotoxic activities with IC50 values between 20 and 40 μM. Further in vitro studies revealed that inhibition of sirtuins could be the possible mechanism of action of these molecules.

PROCESS FOR THE PREPARATION OF QUETIAPINE FUMARATE

The present invention relates to an improved process for the preparation of quetiapine and pharmaceutically acceptable salts. It also relates to improved process for the preparation of intermediates of quetiapine.

An Improved and single pot process for the production of quetiapine hemifumarate substantially free from potential impurities

An improved and single pot process for the preparation of Quetiapine hemifumarate (1), an antipsychotic drug, free from potential impurities is reported with an overall yield of 80%. The reported process for its preparation suffers from the drawback of producing potential impurities identified as 11-piperazin-1- yldibenzo[b,f][1,4]thiazepine (6), 2-(4-dibenzo[b,f][1,4] thiazepin-11- ylpiperazin-1-yl)ethanol (10), dimer (9), and N-methyl- Nphenyldibenzo[ b,f][1,4]thiazapine-11-amine (14). Elimination of these impurities in the process is achieved by chlorination of 3 followed by in situ condensation of obtained 4 with highly pure 8 and subsequently establishing the pH based workup to obtain free base 2, which is further converted to quetiapine hemifumarate salt free from all these impurities. In this report, different aspects of process development such as scheme selection, optimization of different process parameters, identification, synthesis, origin and control of impurities, and development of an accurate analytical method during the development of a scalable process for quetiapine hemifumarate are discussed.