10527-64-7

Basic information

• Product Name: 2-(4-benzhydrylpiperazin-1-yl)ethanol
• Synonyms: 2-(4-benzhydrylpiperazin-1-yl)ethanol;1-Piperazineethanol, 4-(diphenylMethyl)-;1-DIPHENYLMETHYL-4-(2-HYDROXYETHYL)PIPERAZINE(WXG00870)
• CAS NO: 10527-64-7
• Molecular Formula: C₁₉H₂₄N₂O
• Molecular Weight: 296.40666
• Mol File: 10527-64-7.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 180 °C(Press: 0.01 Torr)
• Appearance: /
• Density: 1.115±0.06 g/cm3(Predicted)
• Vapor Pressure: 1.333Pa at 180℃
• PKA: 14.96±0.10(Predicted)
• CAS DataBase Reference: 2-(4-benzhydrylpiperazin-1-yl)ethanol(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(4-benzhydrylpiperazin-1-yl)ethanol(10527-64-7)
• EPA Substance Registry System: 2-(4-benzhydrylpiperazin-1-yl)ethanol(10527-64-7)

Safety Data

• Hazardous Substances Data: 10527-64-7(Hazardous Substances Data)

Usage

General Description

2-(4-benzhydrylpiperazin-1-yl)ethanol, also known as BZPPE, is a chemical compound with potential psychoactive properties. It is a piperazine derivative, which is a class of compounds known to have central nervous system effects. BZPPE is structurally similar to other psychoactive substances like benzylpiperazine (BZP) and mCPP, which are known for their stimulant and hallucinogenic effects. While BZPPE has not been extensively studied, its chemical structure suggests that it may have similar psychoactive properties. However, like BZP and mCPP, BZPPE may also have potential health risks and adverse effects, and its use as a recreational drug is not recommended.

Synthetic route

1-(2-hydroxyethyl)piperazine (103-76-4) + Bromodiphenylmethane (776-74-9) → 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 3.5h;	85.4%

diphenylmethylpiperazine (841-77-0) + 2-bromoethanol (540-51-2) → 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃;	66%
With potassium carbonate In acetone at 60℃;	55%

1-(2-hydroxyethyl)piperazine (103-76-4) + diphenylchloromethane (90-99-3) → 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7)

Conditions	Yield
Stage #1: 1-(2-hydroxyethyl)piperazine With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20℃; Stage #2: diphenylchloromethane In N,N-dimethyl-formamide at 20 - 70℃;	37%
With sodium carbonate; xylene
at 130℃;

1-(2-hydroxyethyl)piperazine (103-76-4) + potassium carbonate (584-08-7) + Bromodiphenylmethane (776-74-9) → 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7)

Conditions	Yield
In N,N-dimethyl-formamide	21.9 g (84.2%)
In N,N-dimethyl-formamide	21.9 g (84.2%)

diphenylmethylpiperazine (841-77-0) + 2-chloro-ethanol (107-07-3) → 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide; toluene at 20℃; Reflux;
With potassium carbonate In N,N-dimethyl-formamide; toluene Reflux;

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) + methyl (E)-3-aminocrotonate (14205-39-1) → β-aminocrotonic acid 1-diphenylmethyl-4-piperazine ester

Conditions	Yield
With triethylamine In chloroform at 50 - 60℃; Solvent; Temperature;	86.3%

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 1-diphenylmethyl-4-(2-chloroethyl)piperazine (79387-51-2)

Conditions	Yield
With thionyl chloride In toluene at 60℃; for 3h;	84%
With thionyl chloride; benzene

+ 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-(4-diphenylmethyl-1-piperazinyl)ethyl acetoacetate (89226-49-3)

Conditions	Yield
at 20 - 80℃; for 6h; Temperature;	72.3%
With triethylamine In chloroform for 10h; Ambient temperature;	59.1%
at 70 - 80℃; for 2h;	739.8 g

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) + cyanoacetic acid (372-09-8) → Cyano-acetic acid 2-(4-benzhydryl-piperazin-1-yl)-ethyl ester

Conditions	Yield
With dicyclohexyl-carbodiimide In tetrahydrofuran at 55℃;	56%

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 3-[2-(4-benzhydryl-piperazino)-ethoxy]-propan-1-ol (102556-29-6)

Conditions	Yield
With thionyl chloride; benzene anschl. Erwaermen mit der Mononatrium-Verbindung des Propan-1,3-diols auf 100grad;

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) + methyl (R)-5-chlorocarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate (88712-56-5, 106463-88-1, 125185-92-4) → methyl (4S)-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate-2-(4-diphenylmethyl-1-piperazinyl)ethyl ester hydrochloride (89226-75-5, 119992-99-3, 126229-12-7, 126372-04-1)

Conditions	Yield
With hydrogenchloride 1.) CH2Cl2, 40 min, 0 deg C; Yield given. Multistep reaction;

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) + methyl (R)-5-chlorocarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate (88712-56-5, 106463-88-1, 125185-92-4) → (S)-Manidipine (126451-47-6)

Conditions	Yield
In dichloromethane at 0℃; for 1.5h; Yield given;

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) + methyl (R)-5-chlorocarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate (88712-56-5, 106463-88-1, 125185-92-4) → (-)-manidipine dihydrochloride (89226-75-5, 119992-99-3, 126229-12-7, 126372-04-1)

Conditions	Yield
With hydrogenchloride 1.) CH2Cl2, 0 deg C; Yield given. Multistep reaction;

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) + C16H16N3O5(1-)*Na(1+) + trichloromethyl chloroformate (503-38-8) → 6-Methyl-4-(2-nitro-phenyl)-2-oxo-3,4-dihydro-2H-pyrimidine-1,5-dicarboxylic acid 1-[2-(4-benzhydryl-piperazin-1-yl)-ethyl] ester 5-cyclopropylmethyl ester (121484-73-9)

Conditions	Yield
1.) Et3N, THF, -23 deg C, 30 min 2.) THF, 0 deg C; Yield given. Multistep reaction;

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-(4-diphenylmethyl-1-piperazinyl)ethyl 2-(3-nitrobenzylidene)acetoacetate (90120-00-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 59.1 percent / Et3N / CHCl3 / 10 h / Ambient temperature 2: 22.8 percent / piperidinium acetate / benzene / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: piperidine / benzene / 5 h / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-Amino-6-methyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-(1-benzhydryl-azetidin-3-yl) ester 5-[2-(4-benzhydryl-piperazin-1-yl)-ethyl] ester

Conditions	Yield
Multi-step reaction with 3 steps 1: 59.1 percent / Et3N / CHCl3 / 10 h / Ambient temperature 2: 22.8 percent / piperidinium acetate / benzene / Ambient temperature 3: 23.9 percent / sodium methoxide / propan-2-ol / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-(4-diphenylmethyl-1-piperazinyl)ethyl 3-aminocrotonate (90096-33-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 20 percent NH3/EtOH View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 3-methyl 5-[2-(4-benzhydryl-1-piperazinyl)-ethyl] (+)-1,4-dihydro-2,6-dimethyl-4-(2-chlorophenyl)-pyridine-3,5-dicarboxylate (89226-62-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 30.8 percent / propan-2-ol / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-(4-benzhydryl-1-piperazinyl)ethyl ethyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (89226-53-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 30.7 percent / propan-2-ol / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-(4-diphenylmethyl-1-piperazinyl)ethyl methyl 2,6-dimethyl-4-(3-nitrophenyl)-3,5-dicarboxylate (104305-93-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 20 percent NH3/EtOH 3: 17.8 percent / propan-2-ol / 6 h / Heating 4: 90.1 percent / 2 N HNO3 / dioxane / 1.5 h / 70 °C View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-(4-benzhydryl-1-piperazinyl)ethyl ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (89226-51-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 48.3 percent / propan-2-ol / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 5-<2-(4-diphenylmethyl-1-piperazinyl)ethyl> 3-ethyl 2-amino-5-methyl-4-(3-nitrophenyl)-4H-pyran-3,5-dicarboxylate (104305-92-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 71 percent / piperidine / propan-2-ol / 4 h / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-(4-benzhydryl-1-piperazinyl)ethyl 2-methoxyethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (90095-79-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 19.5 percent / propan-2-ol / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 4-Benzo[1,2,5]oxadiazol-4-yl-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-[2-(4-benzhydryl-piperazin-1-yl)-ethyl] ester 5-methyl ester; hydrochloride (90096-10-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 45 percent / propan-2-ol / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → Manidipine dihydrochloride (89226-75-5, 119992-99-3, 126229-12-7, 126372-04-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 20 percent NH3/EtOH 3: 17.8 percent / propan-2-ol / 6 h / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-(4-benzhydryl-1-piperazinyl)ethyl methyl 4-(3-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (89226-71-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 28.3 percent / propan-2-ol / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-(4-diphenylmethyl-1-piperazinyl)ethyl ethyl 4-(3-chlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (90095-77-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 43.3 percent / propan-2-ol / 6 h / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 2-(4-benzhydryl-1-piperazinyl)ethyl methyl 2,6-dimethyl-4-(3-trifluoromethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylate (90095-76-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 52.5 percent / propan-2-ol / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → manidipine (89226-50-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: piperidine / benzene / 5 h / Heating 3: propan-2-ol / 7 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: 75.2 percent / propan-2-ol / 6 h / Heating View Scheme

1-diphenylmethyl-4-(2-hydroxyethyl)piperazine (10527-64-7) → 5-<2-(4-diphenylmethyl-1-piperazinyl)ethyl> 3-ethyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (98290-99-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 739.8 g / 2 h / 70 - 80 °C 2: piperidine / benzene / 5 h / Heating 3: 60.5 percent / Na / ethanol / 0.08 h / Heating View Scheme

Upstream product

• 103-76-4 1-(2-hydroxyethyl)piperazine 
• 90-99-3 diphenylchloromethane 
• 841-77-0 diphenylmethylpiperazine 
• 540-51-2 2-bromoethanol 
• 584-08-7 potassium carbonate 
• 776-74-9 Bromodiphenylmethane 
• 107-07-3 2-chloro-ethanol 

Downstream Products

• 79387-51-2 1-diphenylmethyl-4-(2-chloroethyl)piperazine 
• 102556-29-6 3-[2-(4-benzhydryl-piperazino)-ethoxy]-propan-1-ol 
• 89226-49-3 2-(4-diphenylmethyl-1-piperazinyl)ethyl acetoacetate 
• 89226-50-6 manidipine 
• 1418018-38-8 1-(2-azidoethyl)-4-benzhydrylpiperazine 
• 1418018-26-4 {1-[2-(4-benzhydrylpiperazin-1-yl)ethyl]-5-iodo-1H-[1,2,3]triazol-4-yl}methanol 
• 1147699-78-2 2-(4-benzhydrylpiperazin-1-yl)ethyl 5-(cyclopentyloxy)-4-(2-methoxyphenyl)-2-methyl-1,6-naphthyridine-3-carboxylate 
• 90096-34-7 2-(4-[Bis-(4-fluoro-phenyl)-methyl]-piperazin-1-yl)-ethanol 
• 102556-43-4 3-[2-(4-benzhydryl-piperazino)-ethoxy]-propane-1,2-diol 
• 98290-99-4 5-<2-(4-diphenylmethyl-1-piperazinyl)ethyl> 3-ethyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate 
• 90095-76-4 2-(4-benzhydryl-1-piperazinyl)ethyl methyl 2,6-dimethyl-4-(3-trifluoromethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylate 
• 90095-77-5 2-(4-diphenylmethyl-1-piperazinyl)ethyl ethyl 4-(3-chlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate 
• 89226-71-1 2-(4-benzhydryl-1-piperazinyl)ethyl methyl 4-(3-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate 
• 89226-75-5 Manidipine dihydrochloride 

Relevant articles and documents

Preparation method of manidipine hydrochloride

The invention discloses a preparation method of manidipine hydrochloride and belongs to the technical field of medicine preparation. Piperazine serving as a starting raw material is used for synthesis of N-(2-hydroxyethyl)piperazine, then 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine is synthesized, and 2-(4-diphenylmethyl-1-piperazinyl)ethyl acetoacetic ester is synthesized; 2-(4-diphenylmethyl-1-piperazinyl)ethyl acetoacetic ester, m-nitrobenzaldehyde and methyl 3-aminocrotonate are dissolved in isopropanol, the mixture is subjected to heating reflux, a solvent is removed through steaming, residues are dissolved in trichloromethane, the mixture is dried with anhydrous sodium sulfate and filtered, a solvent of the filtrate is recovered under reduced pressure, residues are mixed with methanol to be completely dissolved, hydrogen chloride is introduced in an ice bath, the solvent is removed through steaming, residues are mixed with methanol, activated carbon is added for decoloration, filtering is performed, filtrate is cooled, and manidipine hydrochloride is obtained. The preparation method of manidipine hydrochloride is simple in process, the yield is high, the cost is low, and the product purity is high.

Polymorphic Forms of Manidipine

The invention relates to various new polymorphic forms of manidipine and pharmaceutically acceptable salts thereof. The invention also relates to processes for the preparation of the polymorphic forms of manidipine and pharmaceutically acceptable salts thereof.

Synthesis, Structure-activity relationship, and mode-of-action studies of antimalarial reversed chloroquine compounds

We have previously shown that a "reversed chloroquine (RCQ)" molecule, composed of a chloroquine-like moiety and a resistance reversal-like moiety, can overcome chloroquine resistance in P. falciparum (Burgess, S. J.; Selzer, A.; Kelly, J. X.; Smilkstein, M. J.; Riscoe, M. K.; Peyton, D. H. J. Med. Chem. 2006, 49, 5623. Andrews, S.; Burgess, S. J.; Skaalrud, D.; Kelly, J. X.; Peyton, D. H. J. Med. Chem. 2010, 53, 916). Here, we present an investigation into the Structure-activity relationship of the RCQ structures, resulting in an orally active molecule with good in vitro and in vivo antimalarial activity. We also present evidence of the mode of action, indicating that the RCQ molecules inhibit hemozoin formation in the parasite's digestive vacuole in a manner similar to that of chloroquine.