1191901-07-1

Basic information

• Product Name: Brexpiprazole Intermediate 1
• Synonyms: Brexpiprazole Intermediate 1;tert-butyl 4-(benzo[b]thiophen-4-yl)piperazine-1-carboxylate;4-Benzo[b]thien-4-yl-1-piperazinecarboxylic acid 1,1-dimethylethyl ester;Aripiprazole-Impurity 9
• CAS NO: 1191901-07-1
• Molecular Formula: C17H22N2O2S
• Molecular Weight: 318.43378
• Mol File: 1191901-07-1.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 458.1±35.0 °C(Predicted)
• Appearance: /
• Density: 1.208±0.06 g/cm3(Predicted)
• PKA: 0.20±0.70(Predicted)
• CAS DataBase Reference: Brexpiprazole Intermediate 1(CAS DataBase Reference)
• NIST Chemistry Reference: Brexpiprazole Intermediate 1(1191901-07-1)
• EPA Substance Registry System: Brexpiprazole Intermediate 1(1191901-07-1)

Safety Data

• Hazardous Substances Data: 1191901-07-1(Hazardous Substances Data)

Usage

Uses

Tert-butyl 4-(benzo[b]thiophen-4-yl)piperazine-1-carboxylate is an impuriity of Brexpiprazole(B677385). Brexpiprazole is a drug candidate useful in treatment and prevention of mental disorders including CNS disorders.

Upstream product

• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 1096535-48-6 tert-butyl 4-(3-chloro-2-formylphenyl)piperazine-1-carboxylate 
• 387-45-1 2-chloro-6-fluorobenzaldehyde 
• 5118-13-8 4-bromobenzo[b]thiophene 
• 3610-02-4 4-hydroxybenzothiophene 
• 195520-04-8 benzo[b]thiophen-4-yl trifluoromethanesulfonate 
• 66490-33-3 4-chlorobenzothiophene 

Downstream Products

• 913611-97-9 Brexpiprazole 

Relevant articles and documents

Delineating an alternate convergent synthesis of brexpiprazole: a novel use of commercial 6,7-dihydrobenzo[b]thiophen-4(5H)-one as precursor to an efficacious Buchwald–Hartwig amination step

Abstract: Brexpiprazole – an anti-psychotic drug approved for the treatment of schizophrenia – has been synthesized via an extremely concise and convergent route, which involves in essence two key C–N bond formation (amination) steps that serve to link the piperazine core between the constituent benzo[b]thiophene and 7-butoxyquinolin-2(1H)-one fragments. The highlight of this synthesis is the first amination step, which was effected quite efficaciously by a novel palladium mediated Buchwald–Hartwig coupling between N-Boc-piperazine and the triflate ester of benzo[b]thiophen-4-ol (conveniently prepared in three steps from commercially available 6,7-dihydrobenzo[b]thiophen-4(5H)-one). Indeed, even without an extensive screening of catalysts, ligands and reaction conditions, this amination step could be performed quite efficiently with merely 1?mol% catalyst loading, which cleanly afforded in 87% overall yield 1-(benzo[b]thiophen-4-yl)piperazine—the starting material for the second C–N bond formation and the final step in the synthesis of Brexpiprazole. Graphical Abstract: Synopsis An alternate convergent synthesis of the anti-psychotic drug Brexpiprazole has been described. In particular, a novel palladium catalyzed Buchwald–Hartwig coupling of N-Boc-piperazine with benzo[b]thiophen-4-yl trifluoromethanesulfonate (prepared from commercially available 6,7-dihydrobenzo[b]thiophen-4(5H)-one) has been shown to furnish 1-(benzo[b]thiophen-4-yl)piperazine (a key intermediate in the synthesis of the API) in excellent yield even with 1?mol% catalyst loading. [Figure not available: see fulltext.].

Solvent-free mechanochemical Buchwald-Hartwig amination of aryl chlorides without inert gas protection

A solvent-free Buchwald-Hartwig amination had been developed under high-speed ball-milling conditions, which afforded the desired products with moderate to high yields. The addition of sodium sulfate was found to be crucial for improving both the performance and the reproducibility. Comparative solvent-free stirring experiments implicated the importance of mechanical interaction for the transformation, and the inert gas was proved to be unnecessary for this amination.

METHODS FOR PREPARING BREXPIPRAZOLE, KEY INTERMEDIATES THEREOF AND SALTS THEREOF

The present invention relates to the methods for preparing brexpiprazole, the analogs, key intermediates, and salts thereof, specifically, the present invention relates to a new method for preparing brexpiprazole, the analogs, key intermediates, and salts thereof, and the key intermediates, and salts thereof provided during the preparation. The preparation method has a mild reaction condition, stable intermediate, easy operation, and uses cheap and easy-to-get reagents, thus it saves the synthesis cost, shortens the production cycle, improves the yield and product quality, and is suitable for mass production.