11-(PIPERAZIN-1-YL)DIBENZO[B,F][1,4]THIAZEPINE Chemical Properties

Boiling point:

465.2±55.0 °C(Predicted)

Density 

1.30

storage temp. 

Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

solubility 

DMF: 16 mg/mL; DMSO: 3 mg/mL; Ethanol: 5 mg/mL; PBS (pH 7.2): 0.25 mg/mL

form 

A solid

pka

8.55±0.10(Predicted)

Safety Information

HazardClass 

IRRITANT

11-(PIPERAZIN-1-YL)DIBENZO[B,F][1,4]THIAZEPINE Usage And Synthesis

Chemical Properties

Pale-Yellow Solid

Uses

11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine is a metabolite of Quetiapine, a Benzothiazepine with mixed serotonin and dopamine receptor antagonistic properties used as an antipsychotic.

Definition

ChEBI: Norquetiapine is a dibenzothiazepine.

Synthesis

General procedure for the synthesis of 11-(1-piperazinyl)dibenzo[b,f][1,4]thiazepine from 11-(piperazin-1-yl)dibenzo[b,f][1,4]thiazepine hydrochloride: a toluene solution of 11-chloro-dibenzo[b,f][1,4]thiazepine (1500 mL, 0.686 mol) was mixed with 1500 mL of deionized water and 90 mL of HCl (32% w/w) were mixed. The reaction mixture was heated to 70 °C and stirred for 45 min. Stirring was stopped and allowed to stand for 30 minutes for phase separation. The lower aqueous phase was separated, which contained the HCl salt of 11-piperazin-1-yl dibenzo[b,f][1,4]thiazepine. Subsequently, the aqueous phase was treated with 1000 mL of toluene and 99 g aqueous NaOH (47% w/w). The mixture was heated to 70 °C and stirred for 45 min. Stirring was stopped and allowed to stand for 30 min for phase separation. The lower aqueous phase was discarded, the upper organic phase was retained and 300 mL of deionized water was added to it. The mixture was stirred for 15 minutes and then allowed to stand for 30 minutes. The aqueous phase was discarded and the organic phase was again extracted with 300 mL of deionized water. Approximately 750 mL of toluene was removed by distillation and the concentrate was cooled to 60°C. 200 mL of methyl tertiary butyl ether (MTBE) was added. The mixture was cooled to room temperature and inoculated with Type A crystalline seed. Subsequently, the mixture was cooled to 10 °C and kept under slow stirring for 3 hours. The solid product was separated by filtration through a #3 sintered funnel. The solid was washed with 120 mL of MTBE at room temperature and finally dried under vacuum at 40 °C to give 175 g (86.4% yield) of crystalline product.HPLC analysis showed a product purity of 99.9% w/w.

References

[1] Patent: WO2006/73360, 2006, A1. Location in patent: Page/Page column 10-11
[2] Patent: WO2006/73360, 2006, A1. Location in patent: Page/Page column 10
[3] Patent: WO2007/62338, 2007, A2. Location in patent: Page/Page column 13-14
[4] Patent: WO2007/62337, 2007, A2. Location in patent: Page/Page column 13-14
[5] Patent: WO2007/62337, 2007, A2. Location in patent: Page/Page column 14

11-(PIPERAZIN-1-YL)DIBENZO[B,F][1,4]THIAZEPINE(5747-48-8)Related Product Information

• Quetiapine
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• 11-(1-PIPERAZINYL)-DIBENZO[B,F][1,4]THIAZEPIN HYDROCHLORIDE
• N-DES[2-(2-HYDROXYETHOXY)ETHYL] QUETIAPINE-D8
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• 11-(1-Piperazinyl)-dibenzo[b,f][1,4]thiazepine dihydrochloride
• QUETIAPINE SULFOXIDE
• 11-(1-Piperazinyl-d8)-dibenzo[b,f][1,4]thiazepin-7-ol
• 11-[4-(2-CHLORO-ETHYL)-PIPERAZIN-1-YL]-DIBENZO[B,F][1,4]THIAZEPINE
• 7-Hydroxy Quetiapine-D8
• 7-HYDROXY QUETIAPINE
• CLOTHIAPINE
• Quetiapine fumarate
• 11-(1-PIPERAZINYL)-DIBENZO[B,F][1,4]THIAZEPIN-7-OL