84163-77-9

Usage

Chemical Properties

White Crystalline Powder

Uses

An Intermediate in the synthesis of risperidone and iloperidone.

InChI:InChI=1/C12H13FN2O/c13-9-1-2-10-11(7-9)16-15-12(10)8-3-5-14-6-4-8/h1-2,7-8,14H,3-6H2

Upstream product

• 84162-80-1 4-(2,4-difluorobenzoyl)-1-piperidinecarboxaldehyde 
• 498-94-2 isonipecotic acid 
• 84163-42-8 1-Formylisonipecotic acid 
• 84163-43-9 1-formylisonipecotoyl chloride 
• 84162-86-7 (2,4-difluorophenyl)(4-piperidinyl)methanone 
• 345660-50-6 tert-butyl 4-(6-fluorobenzo[d]isoxazol-3-yl)piperidine-1-carboxylate 
• 467423-44-5 tert-butyl 4-(chloro(hydroxyimino)methyl)piperidine-1-carboxylate 
• 84163-46-2 (2,4-difluorophenyl)(4-piperidinyl)methanone oxime 
• 84162-94-7 1-formyl-4-(2,4-difluorobenzoyl)piperidine oxime 
• 84163-41-7 6-fluoro-3-(1-formyl-4-piperidinyl)-1,2-benzisoxazole 
• 84162-82-3 1-[4-(2.4-Difluoro-benzoyl)-piperidin-1-yl]-ethanone 
• 135634-18-3 (2,4-difluorophenyl)-piperidin-4-yl-methanone oxime hydrochloride 
• 372-18-9 1,3-Difluorobenzene 
• 59084-16-1 1-acetylpiperidine-4-carbonyl chloride 

Downstream Products

• 133454-57-6 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-hydroxyphenyl]ethanone 
• 133455-04-6 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy]-3-methoxyphenyl]propanone 

Relevant academic research and scientific papers

Synthesis of benzoisoxazole derivatives and evaluation of inhibitory potency against cholinesterase for Alzheimer's disease therapeutics

To improve Alzheimer's disease (AD) therapeutics, we have designed and synthesized new benzoisoxazole derivatives that are potent inhibitors of cholinesterase (acetylcholinesterase [AChE] and butyrylcholinesterase [BuChE]). Since inhibition of cholinesterase (ChE) is still considered to be one of the most effective ways of treating AD patients, many new classes of ChE inhibitors have been synthesized. To identify a new type of cholinergic drug, the benzoisoxazole moiety which is the pharmacophore moiety of Risperidone was coupled with natural antioxidants. Some benzoisoxazole derivatives (26-28 and 30) were found to effectively inhibit BuChE (IC50 50 = 8.4 ±0.1 μM). The new benzoisoxazole derivatives showing BuChE inhibitory activity represent a new class of ChE inhibitor and can be used to create novel compound derivative drugs for treating AD patients.

1,3- and 1,4-Benzdiyne equivalents for regioselective synthesis of polycyclic heterocycles

We have devised a novel 1,3-benzdiyne equivalent, capable of quadruple functionalization by sequential benzyne generation and reaction with arynophiles. The key features of this method include the chemoselective generation of two triple bonds in a single benzene ring under fluoride-mediated mild conditions, and the regiocontrol of each benzyne reaction by the substituent next to the triple bond. This method produced various benzo-fused heteroaromatic compounds via reactions with arynophiles, such as furans, azides, and diazo compounds. A validation of the method is given in the convergent synthesis of the antipsychotic drug risperidone. A similar strategy has also been applied to a 1,4-benzdiyne equivalent to construct linearly benzo-fused heteroaromatics.

In silico docking studies and synthesis of new phosphoramidate derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole as potential antimicrobial agents

A new class of phosphoramidate derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole were synthesized in good to excellent yields (78–96%) by an in situ, three-step process. All the synthesized molecules were evaluated for anti-bacterial and anti-fungal activities using in?vitro and in silico methods. The results revealed that the compounds 4b, 4d, 4h, 4i, and 4j exhibited the most promising anti-bacterial activity against S. aureus, B. subtilis, K. pneumoniae, S. typhi and P. mirabilis and anti-fungal activity against A. niger and A. flavus when compared with the standard drugs Norfloxacin and Nystatin at concentrations of 25, 50, 75 and 100 μg/mL. The rest of the title compounds have shown moderate activity against all the bacterial and fungal strains. Molecular docking studies revealed that the synthesized compounds have exhibited significant binding modes with high dock scores ranging from ?7.2 to ?9.5 against 3V2B protein when compared with the standard drugs Norfloxacin (?5.8) and Nystatin (?6.6) respectively. Hence, it is suggested that the synthesized phosphoramidate derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole will stand as the promising antimicrobial drug candidates in future.

Synthesis and characterization of new thiourea and urea derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d] isoxazole: In vitro Antimicrobial and Antioxidant activity

A new class of antimicrobial and antioxidant agents, based on thiourea and urea derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d] isoxazole were synthesized by adopting a simple and efficient method. Synthesized compounds were characterized by spectral data of IR, 1H, 13C NMR and mass spectra. The compounds were evaluated for their efficacy as antimicrobial and antioxidant agents. A few compounds showed good antibacterial, antifungal and antioxidant activity when compared to standard drugs and thus represent a new class of promising lead compounds.

Purification method of 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole hydrochloride

The invention discloses a purification method of a risperidone intermediate 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole hydrochloride as shown in a formula II, which is characterized by comprising the following steps: adding 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole hydrochloride into ethanol, adding a certain amount of water, and carrying out heating reflux until the solution is clear to obtain the risperidone intermediate 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole hydrochloride; and cooling the compound to a certain temperature for crystal growing, then cooling the mixture to -5 to 10 DEG C, and filtering and drying the mixture to obtain the crystal. According to the purification method of the 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole hydrochloride, the dimer shown as the formula V can be effectively separated out, the purification yield is 85% or above, the chemical purity of a finished product can reach 99.9% or above, an amplification effect cannot be generated in large-scale production, and the process is stable.

Reformulating a Pharmacophore for 5-HT2A Serotonin Receptor Antagonists

Several pharmacophore models have been proposed for 5-HT2A serotonin receptor antagonists. These typically consist of two aromatic/hydrophobic moieties separated by a given distance from each other, and from a basic amine. Although specified distances might vary, the models are relatively similar in their general construction. Because our preliminary data indicated that two aromatic (hydrophobic) moieties might not be required for such action, we deconstructed the serotonin-dopamine antipsychotic agent risperidone (1) into four smaller structural fragments that were thoroughly examined in 5-HT2A receptor binding and functional (i.e., two-electrode voltage clamp (TEVC) and intracellular calcium release) assays. It was apparent that truncated risperidone analogues behaved as antagonists. In particular, 6-fluoro-3-(1-methylpiperidin-4-yl)benzisoxazole (4) displayed high affinity for 5-HT2A receptors (Ki of ca. 12 nM) relative to risperidone (Ki of ca. 5 nM) and behaved as a potent 5-HT2A serotonin receptor antagonist. These results suggest that multiple aromatic (hydrophobic) moieties are not essential for high-affinity 5-HT2A receptor binding and antagonist activity and that current pharmacophore models for such agents are very much in need of revision.

Flow Synthesis in Hot Water: Synthesis of the Atypical Antipsychotic Iloperidone

Inductively heated steel reactors continuously perform organic transformations in water under high temperature conditions, utilizing the unique physiochemical properties of water at subcritical conditions. We demonstrated the power of this set-up in the continuous synthesis of the atypical antipsychotic drug iloperidone, in which we performed four out of five steps under aqueous conditions.

Aralkylpiperidine (or piperazinecarboxylic) and its derivatives used for treating hypercalcemia schinzopherenia

PROBLEM TO BE SOLVED: To provide an agent for treating schizophrenia and related neuropsychiatric diseases.SOLUTION: This invention provides an aralkylpiperidine (or piperazine) derivative represented by formula (1), where A ring is a 5-7 membered heterocycle including N, with the heterocycle including a hetero atom arbitrarily selected from O, S, N; X is O, an amino group or a substituted amino group; Z is CH, N or C; Y is O, N or S; n is an integer of 1-5; and R1-R6 are H, a C1-C4 alkyl group or the like.

Palladium-catalyzed benzo[d]isoxazole synthesis by C-H activation/[4 + 1] annulation

We report a palladium-catalyzed intermolecular [4 + 1] annulation pathway for N-phenoxyacetamides with aldehydes to form 1,2-benzisoxazoles. By activating the C-H bonds ortho to phenol-derived O-N bonds, the method enables the simultaneous construction of C-C and CN bonds in 1,2-benzisoxazoles with the O-N bonds intact. The method has been successfully applied to the synthesis of active pharmaceutical intermediates, such as risperidone.

Processes for the preparation of paliperidone

The present invention relates to a novel process for the preparation of paliperidone and its intermediates and also relates to an improved process for the preparation of paliperidone compound of formula (I).