57061-71-9

Usage

Uses

Used in Pharmaceutical Industry:
1-(2-CHLOROETHYL)-4-[3-(TRIFLUOROMETHYL)PHENYL]PIPERAZINE DIHYDROCHLORIDE is used as a precursor in the synthesis of potential anti-cancer and anti-tumor agents due to its unique chemical structure that can be modified to target specific biological pathways involved in cancer and tumor growth.
Used in Research and Development:
In the field of neuroscience, 1-(2-CHLOROETHYL)-4-[3-(TRIFLUOROMETHYL)PHENYL]PIPERAZINE DIHYDROCHLORIDE serves as a research chemical, aiding in the study of neurotransmitters and their receptors. This helps in understanding the mechanisms of various neurological disorders and developing targeted therapies.
Used in Anti-inflammatory and Analgesic Applications:
1-(2-CHLOROETHYL)-4-[3-(TRIFLUOROMETHYL)PHENYL]PIPERAZINE DIHYDROCHLORIDE is being investigated for its potential as an anti-inflammatory and analgesic agent. Its unique chemical properties may offer new avenues for managing pain and inflammation, potentially leading to the development of novel therapeutic agents for these conditions.

Synthetic route

N-2-hydroxyethyl-N'-(3-trifluoromethylphenyl)-piperazine (40004-29-3) → 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9)

Conditions	Yield
With thionyl chloride In dichloromethane for 2h; Reagent/catalyst; Solvent; Cooling with ice; Reflux;	96%
With thionyl chloride In 1,2-dichloro-ethane at 20 - 80℃; for 4h; Temperature; Large scale;	88%

1-Bromo-2-chloroethane (107-04-0) + 1-(3-Trifluoromethylphenyl)piperazine (15532-75-9) → 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9)

Conditions	Yield
With sodium hydroxide In acetone at 20℃; for 48h;	79%
With sodium carbonate In N,N-dimethyl-formamide for 22h; Ambient temperature;
Stage #1: 1-(3-Trifluoromethylphenyl)piperazine With sodium hydroxide In dimethyl sulfoxide for 0.166667h; Stage #2: 1-Bromo-2-chloroethane In dimethyl sulfoxide for 24h;

2-chloro-1-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethanone → 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether at 40℃; for 0.5h;	60%

3-trifluoromethylaniline (98-16-8) + tris-(2-chloroethyl)amine hydrochloride (817-09-4) → 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9)

Conditions	Yield
With potassium carbonate In butan-1-ol at 115 - 120℃; for 22h; Time;	52.8%

tris-(2-chloro-ethyl)-amine (555-77-1) + 3-trifluoromethylaniline (98-16-8) → 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9)

Conditions	Yield
With potassium carbonate In butan-1-ol at 115 - 120℃; for 24h;	45.9%

1-Bromo-2-chloroethane (107-04-0) + 1-(3-Trifluoromethylphenyl)piperazine (15532-75-9) → 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) + 4,4'-bis-(3-trifluoromethyl-phenyl)-1,1'-ethane-1,2-diyl-bis-piperazine (51299-16-2)

Conditions	Yield
In toluene for 6h; Alkylation; Heating;

1-Bromo-2-chloroethane (107-04-0) + 1-[3-(trifluoromethyl)phenyl]piperazine hydrochloride → 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9)

Conditions	Yield
With triethylamine In hexane; dichloromethane
With triethylamine In hexane; dichloromethane
With triethylamine In dichloromethane for 9h; Heating / reflux;
With triethylamine In hexane; dichloromethane

1-[3-(trifluoromethyl)phenyl]piperazine hydrochloride → 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / acetone / 4 h / 20 - 60 °C / Large scale 2: thionyl chloride / 1,2-dichloro-ethane / 4 h / 20 - 80 °C / Large scale View Scheme

4H-pyrido[3,2-b][1,4]oxazin-3-one (20348-09-8) + 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 4-{2-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-4H-pyrido[3,2-b][1,4]oxazin-3-one

Conditions	Yield
With sodium ethanolate In N,N-dimethyl-formamide for 2h; Heating;	92%

1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one (52099-72-6) + 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → BIMT 17 hydrochloride (147359-76-0)

Conditions	Yield
Stage #1: 1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one; 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane With potassium carbonate In dimethyl sulfoxide at 58℃; for 8h; Large scale; Stage #2: With hydrogenchloride In ethanol; water at 65℃; for 2h; Temperature; Large scale;	77%

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) + C9H6NO3(1-)*Na(1+) → 6-Acetyl-3-{2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-3H-benzooxazol-2-one (81522-22-7)

Conditions	Yield
In N,N-dimethyl-formamide for 1h; Heating;	70%

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 1-(2-azidoethyl)-4-(3-trifluoromethylphenyl)piperazine (670234-48-7)

Conditions	Yield
With sodium azide In N,N-dimethyl-formamide at 60℃; for 16h;	67.3%
With sodium azide In N,N-dimethyl-formamide at 50℃; for 10h;

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) + C10H8NO3(1-)*Na(1+) → 6-Propionyl-3-{2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-3H-benzooxazol-2-one (81514-00-3)

Conditions	Yield
In N,N-dimethyl-formamide for 1h; Heating;	62%

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) + C14H7ClNO3(1-)*Na(1+) → 6-(2-Chloro-benzoyl)-3-{2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-3H-benzooxazol-2-one (81533-87-1)

Conditions	Yield
In N,N-dimethyl-formamide for 1h; Heating;	61%

2-ethoxy-1H-benzo[d]imidazole (22219-23-4) + 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → flibanserin

Conditions	Yield
Stage #1: 2-ethoxy-1H-benzo[d]imidazole; 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane With sodium hydroxide In water; isopropyl alcohol at 75℃; for 2h; Stage #2: With hydrogenchloride; isopropyl chloride at 4 - 70℃; for 2h; Temperature;	56.2%

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) + 3-hydroxy-3,4-dihydrobenzotriazine-4-one (28230-32-2) → 3-{2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethoxy}-3H-benzo[d][1,2,3]triazin-4-one

Conditions	Yield
With sodium hydroxide In ethanol for 24h; Substitution; Heating;	40%

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 3-<2-<4-<3-(trifluoromethyl)phenyl>-1-piperazinyl>ethyl>oxazolo<4,5-b>pyridin-2(3H)-one

Conditions	Yield
	40%

3H-benzooxazol-2-one; sodium salt (42142-71-2) + 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 3-{2-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-3H-benzooxazol-2-one (81513-96-4)

Conditions	Yield
In N,N-dimethyl-formamide for 1h; Heating;	38%

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) + C14H8NO3(1-)*Na(1+) → 6-Benzoyl-3-{2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-3H-benzooxazol-2-one (81513-99-7)

Conditions	Yield
In N,N-dimethyl-formamide for 1h; Heating;	37%

2,3-dihydro[1,3]oxazolo[4,5-b]pyridin-2-one (60832-72-6) + 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 3-<2-<4-<3-(trifluoromethyl)phenyl>-1-piperazinyl>ethyl>oxazolo<4,5-b>pyridin-2(3H)-one

Conditions	Yield
With sodium ethanolate 1.) EtOH, RT, 1 h, 2.) DMF, reflux, 1.5 h; Yield given. Multistep reaction;

(E)-5-Benzylidene-6-methyl-(4H)-pyridazin-3-on (26717-37-3) + 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 6-Methyl-5-[1-phenyl-meth-(E)-ylidene]-2-{2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-4,5-dihydro-2H-pyridazin-3-one

Conditions	Yield
With sodium ethanolate 1.) ethanol, reflux, 1 h, 2.) DMF, reflux, 10 h; Yield given. Multistep reaction;

5-(4-Methylbenzylidene)-6-methyl-(4H)-pyridazin-3-on (132372-50-0) + 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 6-Methyl-5-[1-p-tolyl-meth-(E)-ylidene]-2-{2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-4,5-dihydro-2H-pyridazin-3-one

Conditions	Yield
With sodium ethanolate 1.) ethanol, reflux, 1 h, 2.) DMF, reflux, 10 h; Yield given. Multistep reaction;

5-(4-Fluorobenzylidene)-6-methyl-(4H)-pyridazin-3-on (132372-49-7) + 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 5-[1-(4-Fluoro-phenyl)-meth-(E)-ylidene]-6-methyl-2-{2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-4,5-dihydro-2H-pyridazin-3-one

Conditions	Yield
With sodium ethanolate 1.) ethanol, reflux, 1 h, 2.) DMF, reflux, 10 h; Yield given. Multistep reaction;

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethan-1-amine (27144-85-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 67.3 percent / NaN3 / dimethylformamide / 16 h / 60 °C 2: 83.6 percent / PPh3 / tetrahydrofuran; H2O / 2 h / 20 °C View Scheme

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 2-nitro-3-{2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethylamino}phenol (670234-43-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 67.3 percent / NaN3 / dimethylformamide / 16 h / 60 °C 2.1: 83.6 percent / PPh3 / tetrahydrofuran; H2O / 2 h / 20 °C 3.1: K2CO3 / dimethylformamide / 2 h / 50 °C 3.2: 79 percent / 2-(methylsulfonyl)ethanol; NaH / dimethylformamide / 0.5 h / 20 °C View Scheme

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 3,4,5-trihydroxy-6-(2-oxo-1-{2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethyl}-2,3-dihydro-1H-benzoimidazol-4-yloxy)-tetrahydropyran-2-carboxylic acid

Conditions

Yield

Multi-step reaction with 7 steps 1.1: 67.3 percent / NaN3 / dimethylformamide / 16 h / 60 °C 2.1: 83.6 percent / PPh3 / tetrahydrofuran; H2O / 2 h / 20 °C 3.1: K2CO3 / dimethylformamide / 2 h / 50 °C 3.2: 79 percent / 2-(methylsulfonyl)ethanol; NaH / dimethylformamide / 0.5 h / 20 °C 4.1: 80 percent / 1,1,4,7,10,10-Hexamethyltriethylenetetramine; Ag2CO3 / acetonitrile / 0.5 h / 20 °C 5.1: H2 / Pd/C / tetrahydrofuran / 30 h / 20 °C / 3375.27 Torr 6.1: 5.1 g / tetrahydrofuran / 48 h 7.1: 42 percent / aq. LiOH / tetrahydrofuran / 168 h / 20 °C View Scheme

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → (2S,3S,4S,5R,6S)-6-(2-Amino-3-{2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethylamino}-phenoxy)-3,4,5-tris-(2,2-dimethyl-propionyloxy)-tetrahydro-pyran-2-carboxylic acid methyl ester

Conditions

Yield

Multi-step reaction with 5 steps 1.1: 67.3 percent / NaN3 / dimethylformamide / 16 h / 60 °C 2.1: 83.6 percent / PPh3 / tetrahydrofuran; H2O / 2 h / 20 °C 3.1: K2CO3 / dimethylformamide / 2 h / 50 °C 3.2: 79 percent / 2-(methylsulfonyl)ethanol; NaH / dimethylformamide / 0.5 h / 20 °C 4.1: 80 percent / 1,1,4,7,10,10-Hexamethyltriethylenetetramine; Ag2CO3 / acetonitrile / 0.5 h / 20 °C 5.1: H2 / Pd/C / tetrahydrofuran / 30 h / 20 °C / 3375.27 Torr View Scheme

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → methyl 3-[[2-[4-(3-methylphenyl)piperazin-1-yl]ethyl]amino]-2-nitrophenyl-2,3,4-tris-O-(2,2-dimethylpropanoyl)-β-D-glucopyranosiduronate (670234-44-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 67.3 percent / NaN3 / dimethylformamide / 16 h / 60 °C 2.1: 83.6 percent / PPh3 / tetrahydrofuran; H2O / 2 h / 20 °C 3.1: K2CO3 / dimethylformamide / 2 h / 50 °C 3.2: 79 percent / 2-(methylsulfonyl)ethanol; NaH / dimethylformamide / 0.5 h / 20 °C 4.1: 80 percent / 1,1,4,7,10,10-Hexamethyltriethylenetetramine; Ag2CO3 / acetonitrile / 0.5 h / 20 °C View Scheme

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → (2S,3S,4S,5R,6S)-3,4,5-Tris-(2,2-dimethyl-propionyloxy)-6-(2-oxo-1-{2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-2,3-dihydro-1H-benzoimidazol-4-yloxy)-tetrahydro-pyran-2-carboxylic acid methyl ester (670234-49-8)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: 67.3 percent / NaN3 / dimethylformamide / 16 h / 60 °C 2.1: 83.6 percent / PPh3 / tetrahydrofuran; H2O / 2 h / 20 °C 3.1: K2CO3 / dimethylformamide / 2 h / 50 °C 3.2: 79 percent / 2-(methylsulfonyl)ethanol; NaH / dimethylformamide / 0.5 h / 20 °C 4.1: 80 percent / 1,1,4,7,10,10-Hexamethyltriethylenetetramine; Ag2CO3 / acetonitrile / 0.5 h / 20 °C 5.1: H2 / Pd/C / tetrahydrofuran / 30 h / 20 °C / 3375.27 Torr 6.1: 5.1 g / tetrahydrofuran / 48 h View Scheme

1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) + 4-hydroxy-2-mercaptopyrimidine (141-90-2) → C17H19F3N4OS

N,N-dimethylformamide(DMF) + 1,5,6,7-tetrahydro-indol-4-one (13754-86-4) + 1-chloro-2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethane (57061-71-9) → 1-{2-[4-(3-trifluoromethylphenyl)piperazine-1-yl]ethyl}-1,5,6,7-tetrahydroindol-4-one (496921-68-7)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; methanol; hexane; dichloromethane; N,N-dimethyl-formamide
With hydrogenchloride In 1,4-dioxane; methanol; hexane; dichloromethane; N,N-dimethyl-formamide

Upstream product

• 107-04-0 1-Bromo-2-chloroethane 
• 15532-75-9 1-(3-Trifluoromethylphenyl)piperazine 
• 76835-14-8 1-[3-(trifluoromethyl)phenyl]piperazine hydrochloride 
• 98-16-8 3-trifluoromethylaniline 
• 817-09-4 tris-(2-chloroethyl)amine hydrochloride 
• 555-77-1 tris-(2-chloro-ethyl)-amine 
• 40004-29-3 N-2-hydroxyethyl-N'-(3-trifluoromethylphenyl)-piperazine 

Downstream Products

• 670234-48-7 1-(2-azidoethyl)-4-(3-trifluoromethylphenyl)piperazine 
• 1092766-52-3 2-{2-[2-(3-methoxyphenyl)ethyl]phenoxy}ethyl-4-(3'-trifluoromethylphenyl)piperazine 
• 167933-07-5 flibanserin 
• 147359-76-0 BIMT 17 hydrochloride 
• 81513-96-4 3-{2-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-3H-benzooxazol-2-one 
• 1334582-08-9 C₂₁H₂₂F₃N₅ 
• 1334582-18-1 C₂₁H₂₂F₃N₅ 
• 1372157-41-9 1-[2-(5-pyridin-4-yl-[1,3,4]oxadiazol-2-ylsulfanyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine 
• 1372157-40-8 1-{2-[(1-methyl-1H-imidazol-2-yl)thio]ethyl}-4-[3-(trifluoromethyl)phenyl]piperazine 
• 496921-68-7 1-{2-[4-(3-trifluoromethylphenyl)piperazine-1-yl]ethyl}-1,5,6,7-tetrahydroindol-4-one 
• 115762-31-7 1-[2-(4-(3-Trifluoromethylphenyl)piperazin-1-yl)ethylmercapto]-s-triazolo(4,3-a)quinoline 
• 115762-37-3 1-[2-(4-(3-trifluoromethylphenyl)piperazin-1-yl)ethylmercapto]-4-methyl-s-triazolo(4,3-a)quinoline 

Relevant academic research and scientific papers

Preparation method of flibaserin hydrochloride

The invention relates to the technical field of synthesis of medical intermediates, particularly to a preparation method of flibaserin hydrochloride. According to the preparation method, o-phenylenediamine and 3-trifluoromethylphenylpyrazine are used as raw materials; o-phenylenediamine reacts with ethyl acetoacetate to obtain a compound 10-1-G; the 3-trifluoromethylphenylpyrazine compound I is subjected to a two-step substitution reaction to obtain a compound 10-1-B; and the compound 10-1-B and the compound 10-1-G are subjected to a substitution reaction to obtain a final product compound flibaserin hydrochloride. The invention aims to reduce the cost, optimize the process and facilitate industrial production. The method is simple and convenient to operate, reasonable in reaction process,low in production cost, good in product quality, free of environmental pollution and suitable for industrial production, wherein the content of the product is higher than 99.5%.

Benzo-aza-alkyl aryl piperazine derivative and applications in preparation of drugs

The invention discloses a benzo-aza-alkyl aryl piperazine derivative and applications in preparation of drugs. The derivative shows the effect on central nervous systems, especially on the double highaffinity activity of a 5-HT acceptor and a Sigma-1 acceptor. Various physiological and pharmacological effects are brought into play in the body; and the compound can be used as a pharmaceuticalactive substance, especially used for anti-depression, anti-anxiety, anti-bipolar affective disorder and anti-neuropathic pain, and can also be used as an intermediate to prepare other pharmaceuticalactive compounds. The compound is fast in effect and small in toxic and side effect, and can meet demands of clinical applications; and the compound is a compound or a free base or salt thereof havingthe following structural formula (IV). The structure of the compound or the free base or salt thereof is shown as the structural formula (IV).

A new method for synthesizing flibanserin (by machine translation)

The invention relates to a new method for synthesizing of flibanserin, which belongs to the technical field of organic synthesis. The invention respectively in order to triethanolamine and between amino benzotrifluoride as the starting material, to prepare the piperazine intermediate; then to the O-phenylene diamine and the original four carbonate as raw material, the preparation of the ethoxy and imidazole intermediate; the obtained piperazine intermediate and benzimidazole intermediate undergo the substitution reaction, and hydrochloric acid deprotection to obtain the target product of flibanserin. The invention has few synthetic steps, few by-products, intermediate products and the target product yield is relatively high, intermediate product 2 - ethoxy and imidazole yield up 94.2%, the target product yield can reach 56.2%, it can be seen, the invention overcomes the substance in the prior art synthesis step is tedious, and more byproducts, target low yield of product defect. In addition, the present invention has a simple structure, high purity of product, the economic and environmental protection industrial line, has a very wide range of use and potential economic benefits. (by machine translation)

The preparation method of the flibanserin

The invention discloses a preparation method of flibanserin. The preparation method uses trifluoromethylbenzene, triamine (2-halogen ethyl) and ortho-nitroaniline which are easy to obtain as raw materials and adopts classical elementary reactions such as cyclization, substitution, reduction and condensation, so that the flibanserin is prepared. The raw materials of the preparation method are easy to obtain, the technology is succinct, the yield is high, the preparation method is economical and environment-friendly, and a new preparation way is provided for the industrial production of the flibanserin.

Preparation method of flibaserin intermediate

The invention discloses a method belonging to the field of heterocyclic compounds, and concretely relates to a preparation method of a flibaserin intermediate. The preparation method comprises the following steps of (1) dissolving 1-(3-trifluoromethylphenyl) piperazine hydrochloride in a solvent a, and reacting with 2-halogenated ethanol or ethylene oxide in the presence of alkali to obtain 2-(4-(3-trifluoromethylphenyl) piperazine-1-ethanol; (2) reacting the 2-(4-(3-trifluoromethylphenyl) piperazine-1-ethanol with a chloride agent compound to obtain a compound as shown in a formula I. According to the preparation method, the reaction selectivity is improved, the generation of impurities is reduced, the product purity is improved, and the preparation method is simple and convenient to operate, environmentally-friendly, and beneficial for industrialized mass production.

HETEROARYLTHIO COMPOUNDS

Heteroarylthio compounds covalently linked to an arylpiperazine moiety for the treatment of neurological conditions.

TREATMENT OF ORGANOPHOSPHATE EXPOSURE WITH TETRAHYDROINDOLONE ARYLPIPERAZINE COMPOUNDS

A method of treating exposure to organophosphate agents through the use of compounds comprising tetrahydroindolone and arylpiperazine moieties.

2-[(3-Methoxyphenylethyl)phenoxy]-based ABCB1 inhibitors: Effect of different basic side-chains on their biological properties

Recently, 2-[(3-methoxyphenylethyl)phenoxy]-moiety has been selected for the design and synthesis of new small ABCB1 inhibitors. In the present paper, this moiety has been linked through a spacer of 2-5 carbon atoms to the nitrogen of three different basic nuclei such as: (i) N-4-arylpiperazine, (ii) N-4-methylpiperazine, and (iii) 6,7-dimethoxytetrahydroisoquinoline. The results demonstrated that all the selected basic nuclei were well tolerated and that, globally, the best inhibitory activity for each series was obtained when the spacer between the 2-[(3-methoxyphenylethyl)phenoxy] moiety and the basic nucleus consisted of a four-carbon chain. Among the synthesized compounds, N-4-methylpiperazine- 10c (IC50 = 0-15 μM) and tetrahydroisoquinoline-derivatives 11c (IC50 = 0.08 μM) with the spacer n = 4 for both series, displayed the best potency to inhibit ABCB1 activity. Moreover, for each compound, the ABCB1 interacting mechanism has been evaluated by three combined biological assays. N-4-methylpiperazine- (10a-d) and tetrahydroisoquinoline- (11a-d) derivatives were Cyclosporin A-like ABCB1 nontransported substrates.

Microwave-assisted solvent-free synthesis of 3-[(4-substituted piperazin-1-yl)alkyl] imidazo[2,1-b][1,3]benzothiazol-2(3H)-ones as serotonin3 (5-HT3) receptor antagonists

A series of novel 3-[(4-substituted piperazin-1-yl)alkyl]imidazo[2,1-b][1, 3]benzothiazol-2(3H)-ones were prepared by microwave irradiation using alumina as solid support and also by a conventional method. The compounds were characterized by spectral data and the purity was ascertained by microanalysis. The synthesized compounds were evaluated for 5-hydroxytryptamine3 antagonisms in a longitudinal muscle-myenteric plexus preparation from guinea pig ileum against the 5-hydroxytryptamine3 agonist, 2-methyl-5-hydroxytryptamine. Among the test compounds, 3-[2-(4-methylpiperazin- 1-yl)ethyl]imidazo[2,1-6][1,3]benzothiazol-2(3H)-one (3b) showed most favorable 5-hydroxytryptamine3 antagonism (pA2 6.7) in the isolated guinea pig ileum.