23056-29-3

Basic information

• Product Name: N-phenylpiperidin-4-amine
• Synonyms: N-phenylpiperidin-4-amine;Phenyl-Piperidine-4-YL-Amine;n-Phenyl-4-piperidinamine, 98%;Despropionyl norfentanyl;N-Phenyl-4-piperidinamine,98%;phenyl(4-piperidyl)amine;4-Piperidinamine,N-phenyl-;Fentanyl Related Compound B (10 mg) (4-Anilinopiperidine)
• CAS NO: 23056-29-3
• Molecular Formula: C₁₁H₁₆N₂
• Molecular Weight: 176.25814
• EINECS: 245-402-9
• Product Categories: pharmaceutical
• Mol File: 23056-29-3.mol

Chemical Properties

• Boiling Point: 312°Cat760mmHg
• Flash Point: 185.3°C
• Appearance: /
• Density: 1.052g/cm³
• Vapor Pressure: 0.001mmHg at 25°C
• Refractive Index: 1.579
• PKA: 9.83±0.10(Predicted)
• CAS DataBase Reference: N-phenylpiperidin-4-amine(CAS DataBase Reference)
• NIST Chemistry Reference: N-phenylpiperidin-4-amine(23056-29-3)
• EPA Substance Registry System: N-phenylpiperidin-4-amine(23056-29-3)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 23056-29-3(Hazardous Substances Data)

Usage

InChI:InChI=1/C11H16N2/c1-2-4-10(5-3-1)13-11-6-8-12-9-7-11/h1-5,11-13H,6-9H2

Synthetic route

1-(tert-butoxycarbonyl)-4-phenylaminopiperidine (125541-22-2) → phenyl-piperidin-4-yl-amine (23056-29-3)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃; for 1h;	100%
With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 3h;	86%
With trifluoroacetic acid In dichloromethane

N-(1-ethoxycarbonyl-4-piperidinyl)aniline (116512-92-6) → phenyl-piperidin-4-yl-amine (23056-29-3)

Conditions	Yield
With hydrogenchloride In water for 16h; Heating;	92%

4-aminopiperidine (13035-19-3) + chlorobenzene (108-90-7) → 1-phenylpiperidin-4-ylamine (63921-23-3) + 1-phenyl-4-(phenylamino)piperidine + phenyl-piperidin-4-yl-amine (23056-29-3)

Conditions	Yield
With sodium t-butanolate; DavePhos; tris-(dibenzylideneacetone)dipalladium(0) In xylene at 130℃; for 24h;	A 60% B 7% C n/a

4-aminopiperidine (13035-19-3) + bromobenzene (108-86-1) → 1-phenylpiperidin-4-ylamine (63921-23-3) + 1-phenyl-4-(phenylamino)piperidine + phenyl-piperidin-4-yl-amine (23056-29-3)

Conditions	Yield
With chiral ferrocene; sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium(0) In xylene at 130℃; for 24h; Product distribution; Further Variations:; Reagents;	A 18% B 8% C 15%

aniline (62-53-3) + ethane-α.β-bis-sulfonic acid chloride → phenyl-piperidin-4-yl-amine (23056-29-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) molecular sieves; 2) NaBH4 / 1) benzene, reflux, 20 h; 2) EtOH, room temp., 5 h 2: 92 percent / 6 N aq. HCl / H2O / 16 h / Heating View Scheme

N-ethoxycarbonyl-4-piperidone (29976-53-2) → phenyl-piperidin-4-yl-amine (23056-29-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) molecular sieves; 2) NaBH4 / 1) benzene, reflux, 20 h; 2) EtOH, room temp., 5 h 2: 92 percent / 6 N aq. HCl / H2O / 16 h / Heating View Scheme

4-piperidone hydrochloride (41979-39-9) + aniline (62-53-3) → phenyl-piperidin-4-yl-amine (23056-29-3)

Conditions	Yield
Stage #1: 4-piperidone hydrochloride; aniline With acetic acid; zinc at 20 - 70℃; for 24h; Stage #2: With sodium hydroxide In water Product distribution / selectivity; Cooling with ice;

N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3) → phenyl-piperidin-4-yl-amine (23056-29-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tris(acetoxy)borohydride; acetic acid / 1,2-dichloro-ethane / 20 °C 2: trifluoroacetic acid / dichloromethane / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium cyanoborohydride; acetic acid / methanol / 24 h / 20 °C 2: trifluoroacetic acid / dichloromethane / 3 h / 0 - 20 °C View Scheme

aniline (62-53-3) → phenyl-piperidin-4-yl-amine (23056-29-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tris(acetoxy)borohydride; acetic acid / 1,2-dichloro-ethane / 20 °C 2: trifluoroacetic acid / dichloromethane / 1 h / 20 °C View Scheme

4-piperidone hydrochloride (41979-39-9) → phenyl-piperidin-4-yl-amine (23056-29-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 24 h / 20 °C 2: sodium cyanoborohydride; acetic acid / methanol / 24 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 3 h / 0 - 20 °C View Scheme

styrene oxide (96-09-3) + phenyl-piperidin-4-yl-amine (23056-29-3) → 1-phenyl-2-(4-phenylamino-piperidin-1-yl)-ethanol (1269606-71-4)

Conditions	Yield
	85%

1-(3-chloropropoxy)-4-fluorobenzene (1716-42-3) + phenyl-piperidin-4-yl-amine (23056-29-3) → {1-[3-(4-Fluoro-phenoxy)-propyl]-piperidin-4-yl}-phenyl-amine

Conditions	Yield
With potassium carbonate; sodium iodide In 1,4-dioxane for 16h; Heating;	60%

1-isoquinolinecarbonitrile (1198-30-7) + phenyl-piperidin-4-yl-amine (23056-29-3) → N-phenyl-N-(piperidin-4-yl)isoquinoline-1-amine

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; 1,3-dicyano-5-fluoro-2,4,6-tris(diphenylamino)benzene In acetonitrile at 20℃; for 12h; Inert atmosphere; Irradiation;	60%

C14H17Cl3N2O + phenyl-piperidin-4-yl-amine (23056-29-3) → C25H32Cl2N4O + C39H48Cl4N6O2

Conditions	Yield
With potassium carbonate In acetonitrile at 25℃; for 18h;	A 55% B n/a

4-chloro-1-(4-phenylpiperazin-1-yl)butan-1-one + phenyl-piperidin-4-yl-amine (23056-29-3) → C25H34N4O + C39H52N6O2

Conditions	Yield
With potassium carbonate In acetonitrile at 25℃; for 18h;	A 49% B n/a

C15H21ClN2O2 + phenyl-piperidin-4-yl-amine (23056-29-3) → C26H36N4O2 + C41H56N6O4

Conditions	Yield
With potassium carbonate In acetonitrile at 25℃; for 18h;	A 45% B n/a

1-(6-morpholinopyrimidin-4-yl)piperidine-4-carboxylic acid + phenyl-piperidin-4-yl-amine (23056-29-3) → (1-(6-morpholinopyrimidin-4-yl)piperidin-4-yl)(4-(phenylamino)piperidin-1-yl)methanone

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃;	41%

phenyl-piperidin-4-yl-amine (23056-29-3) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 1-(4-Fluoro-phenyl)-4-(4-phenylamino-piperidin-1-yl)-butan-1-one

Conditions	Yield
With potassium carbonate; sodium iodide In 1,4-dioxane for 16h; Heating;	35%

phenyl-piperidin-4-yl-amine (23056-29-3) + 5-({[1-(4-Chloro-phenyl)-methanoyl]-amino}-methyl)-thiophene-2-sulfonyl chloride (166964-34-7) → N-({5-[(4-anilinopiperidin-1-yl)sulfonyl]thien-2-yl}methyl)-4-chlorobenzamide

Conditions

Yield

Stage #1: phenyl-piperidin-4-yl-amine With polymer-bound morpholine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 5-({[1-(4-Chloro-phenyl)-methanoyl]-amino}-methyl)-thiophene-2-sulfonyl chloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 15h; Stage #3: With polymer-bound aminobenzene; polymer-bound isocyanate In dichloromethane; N,N-dimethyl-formamide at 20℃; for 5h;

4-chlorosulfonylbenzoyl chloride (7516-60-1) + phenyl-piperidin-4-yl-amine (23056-29-3) + 4-Br-2-[C(O)O-Wang resin]-aniline → 5-bromo-2-[4-(4-phenylamino-piperidine-1-sulfonyl)-benzoylamino]-benzoic acid

Conditions	Yield
Stage #1: 4-chlorosulfonylbenzoyl chloride; 4-Br-2-[C(O)O-Wang resin]-aniline With pyridine In dichloromethane at 20℃; for 4h; Stage #2: phenyl-piperidin-4-yl-amine With triethylamine In dichloromethane at 20℃; for 15h; Stage #3: With trifluoroacetic acid In dichloromethane at 20℃; for 1h;

6-hydroxy-1H-indole-2-carboxylic acid (40047-23-2) + phenyl-piperidin-4-yl-amine (23056-29-3) → C20H21N3O2

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide for 16h;

phenyl-piperidin-4-yl-amine (23056-29-3) → {1-[3-(4-Fluoro-phenoxy)-propyl]-piperidin-4-yl}-methyl-phenyl-amine

Conditions	Yield
Multi-step reaction with 2 steps 1: 60 percent / K2CO3, NaI / dioxane / 16 h / Heating 2: H2 / 10percent Pd/C / aq. ethanol / 16 h View Scheme

C21H18Cl3F6NO2 + phenyl-piperidin-4-yl-amine (23056-29-3) → C32H33Cl2F6N3O2

Conditions	Yield
With 3 A molecular sieve; sodium cyanoborohydride In CF3CH2OH at 23℃; for 4h;

C20H24N2O2 (1094173-12-2) + phenyl-piperidin-4-yl-amine (23056-29-3) → C31H38N4O (1094173-07-5)

Conditions	Yield
With polymer-supported carbodiimide; benzotriazol-1-ol In N,N-dimethyl-formamide at 50℃;

phenyl-piperidin-4-yl-amine (23056-29-3) + 1-phenyl-2-bromoethane (103-63-9) → (1-Phenethyl-piperidin-4-yl)-phenyl-amine (21409-26-7)

Conditions	Yield
With sodium hydroxide at 120℃; Product distribution / selectivity;

phenyl-piperidin-4-yl-amine (23056-29-3) + cyclopentanone (120-92-3) → (1-cyclopentyl-piperidin-4-yl)-phenyl-amine

Conditions	Yield
With sodium tris(acetoxy)borohydride In dichloromethane

C14H16N2O3S (34330-08-0) + phenyl-piperidin-4-yl-amine (23056-29-3) → C25H30N4O2S (1135023-95-8)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 24h; Inert atmosphere;

phenyl-piperidin-4-yl-amine (23056-29-3) + phenyl isothiocyanate (103-72-0) → C18H21N3S (1620774-22-2)

Conditions	Yield
In toluene at 20℃; for 2h;

phenyl-piperidin-4-yl-amine (23056-29-3) → 1-(2-(methylamino)ethyl)-N-phenylpiperidin-4-amine hydrochloride

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tris(acetoxy)borohydride / dichloromethane / 16 h / 20 °C 2: hydrogenchloride / dichloromethane; 1,4-dioxane / 2 h / 20 °C View Scheme

phenyl-piperidin-4-yl-amine (23056-29-3) + O-tert-butyl N-methyl-N-(2-oxoethyl)carbamate (123387-72-4) → C19H31N3O2

Conditions	Yield
With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 16h;

Upstream product

• 116512-92-6 N-(1-ethoxycarbonyl-4-piperidinyl)aniline 
• 13035-19-3 4-aminopiperidine 
• 108-86-1 bromobenzene 
• 108-90-7 chlorobenzene 
• 62-53-3 aniline 
• 29976-53-2 N-ethoxycarbonyl-4-piperidone 
• 41979-39-9 4-piperidone hydrochloride 
• 125541-22-2 1-(tert-butoxycarbonyl)-4-phenylaminopiperidine 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 

Downstream Products

• 1094173-07-5 C₃₁H₃₈N₄O 
• 21409-26-7 (1-Phenethyl-piperidin-4-yl)-phenyl-amine 
• 1135023-95-8 C₂₅H₃₀N₄O₂S 
• 1269606-71-4 1-phenyl-2-(4-phenylamino-piperidin-1-yl)-ethanol 
• 1620774-22-2 C₁₈H₂₁N₃S 

Relevant articles and documents

Dual targeting of acetylcholinesterase and tau aggregation: Design, synthesis and evaluation of multifunctional deoxyvasicinone analogues for Alzheimer's disease

Development of multitargeted ligands have demonstrated remarkable efficiency as potential therapeutics for Alzheimer's disease (AD). Herein, we reported a new series of deoxyvasicinone analogues as dual inhibitor of acetylcholinesterase (AChE) and tau aggregation that function as multitargeted ligands for AD. All the multitargeted ligands 11(a-j) and 15(a-g) were designed, synthesized, and validated by 1HNMR, 13CNMR and mass spectrometry. All the synthesized compounds 11(a-j) and 15(a-g) were screened for their ability to inhibit AChE, BACE1, amyloid fibrillation, α-syn aggregation, and tau aggregation. All the screened compounds possessed weak inhibition of BACE-1, Aβ42 and α-syn aggregation. However, several compounds were identified as potential hits in the AChE inhibitory screening assay and cellular tau aggregation screening. Among all compounds, 11f remarkably inhibited AChE activity and cellular tau oligomerization at single-dose screening (10 μM). Moreover, 11f displayed a half-maximal inhibitory concentration (IC50) value of 0.91 ± 0.05 μM and half-maximal effective concentration (EC50) value of 3.83 ± 0.51 μM for the inhibition of AChE and cellular tau oligomerization, respectively. In addition, the neuroprotective effect of 11f was determined in tau-expressing SH-SY5Y cells incubated with Aβ oligomers. These findings highlighted the potential of 11f to function as a multifunctional ligand for the development of promising anti-AD drugs.

Pyrimidyl piperazine urea TRPV1 antagonistic/MOR agonistic double-target compound as well as preparation method and application thereof

The invention discloses a pyrimidinyl piperazine urea TRPV1 antagonistic/MOR agonistic double-target compound or a pharmaceutically acceptable salt thereof, the compound has a structural general formula I, and a drug taking the compound as an active component not only shows obvious inhibitory activity on TRPV1, but also can show obvious agonistic activity on MOR. The invention also discloses a preparation method of the compound or the pharmaceutically acceptable salt thereof. The preparation method has the characteristic of mild reaction conditions. The invention also discloses application of the compound or the pharmaceutically acceptable salt thereof in preparation of a medicine for treating and/or preventing TRPV1 and/or MOR mediated diseases, the medicine not only can block pain transmission of peripheral and central nervous systems, but also can reduce side effects related to single targeting, such as nausea, sleepiness and respiratory depression caused by an MOR agonist and nociceptive thermal inductance weakening and obvious body temperature rise caused by a TRPV1 antagonist, and has a good application prospect.

Benzyl piperazine urea TRPV1 antagonistic and MOR agonistic double-target drug as well as preparation method and application thereof

The invention belongs to the technical field of pharmacy, and particularly discloses a benzyl piperazine urea TRPV1 antagonistic and MOR agonistic double-target drug and a preparation method and application thereof, and particularly relates to a compound in general formula (I) and a pharmaceutically acceptable salt thereof, which can be used for preventing and/or treating diseases related to TRPV1 and/or MOR activity. , Immune dysfunction, neurological and psychiatric disorders, respiratory diseases, urinary and reproductive disorders. The invention also relates to a preparation method of the compounds and a pharmaceutical preparation containing the compounds.

Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores

A scalable, cost-efficient and simple synthetic pathway towards potential bivalent opioid/dopamine receptor ligands was developed and optimized. Three novel compounds that contain both opioid and dopamine pharmacophores linked by the four methylene group chain were synthesized in 33, 35 and 39 % overall yield after a four-step synthetic route starting from three commercially available N-aryl piperazines. The anilino piperidine precursor was easily prepared in three steps, as previously published, starting from 4-piperidone. The synthesis presented in this paper could be of interest for heterocyclic and general organic chemistry. The newly designed compounds possessing two pharmacophores, opioid and D2/D3, are potentially useful pharmacological probes. Of particular interest would be the simultaneous binding to both opioid and D2/D3 receptors, and the resulting pharmacological responses may be useful for the further understanding of tolerance and dependence phenomena in opioid clinical use and/or abuse.

NON-PEPTIDIC NEUROPEPTIDE Y RECEPTOR MODULATORS

The invention provides compounds that are modulators of neuropeptide Y (NPY) receptors, which can be selective inhibitors of NPY receptor Y2R. NPY receptor modulatory compounds are of the general formula Ar2-Y-Ar1-W-Ar3, wherein the variables are as defined herein. Compounds of the invention can be used for treatment of malconditions in patients wherein modulation of an NPY receptor is medically indicated, for example including drug or alcohol abuse, anxiety disorders, depression, stress-related disorders, neurological disorders, nerve degeneration, osteoporosis or bone loss, sleep/wake disorders, cardiovascular diseases, obesity, anorexia, inovulation, fertility disorders, angiogenesis, cell proliferation, learning and memory disorders, migraine and pain.

Reduction of hERG inhibitory activity in the 4-piperidinyl urea series of H3 antagonists

Structural features of the substituted 4-piperidinyl urea analogs 1, responsible for the H3 antagonist activity, have been identified. Structure-activity relationship of the H3 receptor affinity, hERG ion channel inhibitory activity and their separation is described. Preliminary pharmacokinetic evaluation of the compounds of the series is addressed.

A METHOD FOR THE PREPARATION OF FENTANYL

The invention provides a method for the preparation of fentanyl comprising: (a) reacting 4-piperidone hydrochloride (NPP) with aniline in presence of reducing environment to produce 4-anilinopiperidine (4- ANPP), (b) alkylating/reacting the 4- ANPP as obtained from step (a) with phenethyl halide under reflux conditions in highly alkaline medium to give 4-anilino-N-phenethylpiperidine, and (c) converting the said 4-anilino-N-phenethylpiperidine to fentanyl by reacting with propionyl chloride in presence of halogenated hydrocarbons then isolating fentanyl by solvent extraction and purified by crystallization from petroleum ether (60-80 °C).

Palladium-mediated N-arylation of heterocyclic diamines: Insights into the origin of an unusual chemoselectivity

The chemoselectivity of the palladium-mediated reaction of bromobenzene with various heterocyclic diamines was studied. Whatever the ligand used, 3-aminopyrrolidine underwent arylation of the secondary amine function (> 82%), whereas the more flexible 3-aminoazepinine was arylated on its primary function (>70%). The ratio "arylation of primary amine versus arylation of secondary amine" of 3-aminopiperidine with bromobenzene varied from 90:10 (BINAP, electron-enriched and hindered biphenyls L2 or L3) to 32:68 with the Josiphos-type ligand L10. The same trend was observed when 4-aminopiperidine was used (82:18 with L2 and 17:83 with L10). This selectivity can be tuned by the choice of aryl halide partners having different steric and electronic properties. A cooperative effect of both nitrogens of diamines during the reaction was deduced from competitive experiments. Finally, 13C and 31P NMR experiments, carried out with 3-aminopyrrolidine at room temperature, support a fast coordination of the primary amine to the metal. Indeed, a palladium complex resulting from the unusual displacement of one phosphane group of the intermediate ArPdX(BINAP) by the primary amino group was characterized.

Dipeptides which promote release of growth hormone

Compounds of formula (I) are growth hormone releasing peptide mimetics which are useful for the treatment and prevention of osteoporosis. STR1

Aminohaloborane in Organic Synthesis. IX. Exclusive ortho Acylation Reaction of N-Monoaminoalkylanilines

The exclusive ortho acylation reaction of aniline derivatives using boron trichloride made possible the one-step synthesis of 2-acyl-N-monoaminoalkylanilines (1) and the corresponding imines (2) from N-monoaminoalkylanilines, even in the case of compounds with a bulky substituent at the nitrogen atom.Conventional methods only give 1 via elaborate procedures.Keywords: regioselective reaction; 2-acylaniline derivative; 2-acylaniline-imine derivative; boron trichloride