53617-35-9

Basic information

• Product Name: 4-(PIPERIDIN-4-YL)-MORPHOLINE
• Synonyms: CHEMBRDG-BB 4004473;4-MORPHOLINOPIPERIDINE;4-(PIPERIDIN-4-YL)-MORPHOLINE;AKOS BB-9182;TIMTEC-BB SBB010091;4-Morpholino-piperidin;4-(PIPERIDIN-4-YL)-MORPHOLINE >98%;4-MORPHOLINO-PIPERDINEDIHYDROCHLORIDE
• CAS NO: 53617-35-9
• Molecular Formula: C₉H₁₈N₂O
• Molecular Weight: 170.25
• EINECS: 1592732-453-0
• Product Categories: Building Blocks;Heterocyclic Building Blocks;Piperidines
• Mol File: 53617-35-9.mol

Chemical Properties

• Melting Point: 40-43 °C(lit.)
• Boiling Point: 100-115 °C0.15-0.20 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: /
• Density: 1.034 g/cm³
• Vapor Pressure: 0.63-4.58Pa at 25-45℃
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: 10.21±0.10(Predicted)
• CAS DataBase Reference: 4-(PIPERIDIN-4-YL)-MORPHOLINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(PIPERIDIN-4-YL)-MORPHOLINE(53617-35-9)
• EPA Substance Registry System: 4-(PIPERIDIN-4-YL)-MORPHOLINE(53617-35-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-20/21/22
• Safety Statements: 26-36-36/37/39
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 53617-35-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-(PIPERIDIN-4-YL)-MORPHOLINE is used as a reactant for the synthesis of selective adenosine A2A receptor antagonists, which are important for the treatment of various neurological disorders, such as Parkinson's disease.
4-(PIPERIDIN-4-YL)-MORPHOLINE is also used as a building block for the development of antidepressant drugs, which help in the treatment of mood disorders, such as major depressive disorder and anxiety.
4-(PIPERIDIN-4-YL)-MORPHOLINE is used as a key intermediate in the synthesis of small molecules that restore E-cadherin expression and reduce invasion in colorectal carcinoma cells, which can help in the development of targeted cancer therapies.
4-(PIPERIDIN-4-YL)-MORPHOLINE is used as a precursor for the development of orally bioavailable P2Y12 antagonists, which are important for the inhibition of platelet aggregation and prevention of thrombotic events.
Used in Chemical Industry:
4-(PIPERIDIN-4-YL)-MORPHOLINE is used as a reactant for the synthesis of quinoline derivatives with antimicrobial activity, which can be employed as effective agents against various bacterial and fungal infections.
4-(PIPERIDIN-4-YL)-MORPHOLINE is also used as a key intermediate in the synthesis of antimalarial drugs, which are crucial for the treatment and prevention of malaria caused by Plasmodium parasites.

InChI:InChI=1S/C9H18N2O/c1-3-10-4-2-9(1)11-5-7-12-8-6-11/h9-10H,1-8H2

Synthetic route

4-(1-benzyl-piperidin-4-yl)-morpholine (415967-79-2) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
With palladium on activated charcoal; hydrogen In isopropyl alcohol at 80℃; under 3750.38 Torr; for 7h; Reagent/catalyst; Autoclave;	100%
With palladium on activated charcoal; hydrogen In methanol at 20℃; under 3750.38 Torr; for 6h;	97.6%
With hydrogen; palladium 10% on activated carbon In methanol at 20℃; under 2585.81 Torr; for 18h;	93%
With hydrogenchloride; Pd(OH)2 In methanol	932 mg (91%)
With hydrogenchloride; Pd(OH)2 In methanol	932 mg (91%)

4-(1-benzylpiperidin-4-yl)morpholine dihydrochloride → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
Stage #1: 4-(1-benzylpiperidin-4-yl)morpholine dihydrochloride With potassium carbonate In tert-butyl alcohol at 60℃; for 0.5h; pH=>11; Stage #2: With palladium 10% on activated carbon In tert-butyl alcohol at 50℃; for 8h; pH=>11;	91.6%
Stage #1: 4-(1-benzylpiperidin-4-yl)morpholine dihydrochloride With potassium carbonate In water; tert-butyl alcohol at 45℃; Industrial scale; Stage #2: With hydrogen In tert-butyl alcohol at 60℃; under 3000.3 Torr; Industrial scale;	88%

tert-butyl 4-(morpholin-4-yl)piperidine-1-carboxylate (125541-20-0) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃; for 6h;	79%
With trifluoroacetic acid In dichloromethane at 20℃; for 2h;
With hydrogenchloride In methanol at 40℃; for 12h;	1.52 g
With trifluoroacetic acid In dichloromethane at 20℃;	3 g

morpholine (110-91-8) + 1-phenylmethyl-4-piperidone (3612-20-2) → 4-(piperidin-4-yl)morpholine (53617-35-9) + 4-(1-benzyl-piperidin-4-yl)-morpholine (415967-79-2)

Conditions	Yield
With 10 wt% Pd(OH)2 on carbon; hydrogen at 80℃; under 3750.38 Torr; for 4h; Reagent/catalyst; Time; Autoclave;	A 19.7% B 77.5%

morpholine (110-91-8) + N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 0 - 20℃; for 16h;	74%
With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 0 - 20℃; for 16h;	74%
Stage #1: morpholine; N-tert-butyloxycarbonylpiperidin-4-one With titanium(IV) isopropylate In tetrahydrofuran at 20℃; for 1h; Stage #2: With sodium cyanoborohydride In tetrahydrofuran; ethanol at 20℃; Stage #3: With water In tetrahydrofuran; ethanol for 0.5h;

4-morpholinopyridine (2767-91-1) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
With hydrogen; ruthenium(IV) oxide

morpholine (110-91-8) + isopropyl alcohol (67-63-0) + N-ethoxycarbonyl-4-piperidone (29976-53-2) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
With potassium hydroxide; sodium borohydrid; toluene-4-sulfonic acid In ethanol; toluene

4-(4-morpholinopiperidin-1-yl)benzonitrile (186650-77-1) → 4-fluorobenzonitrile (1194-02-1) + 4-(piperidin-4-yl)morpholine (53617-35-9)

benzyl 4-morpholin-4-ylpiperidine-1-carboxylate (334942-09-5) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
With hydrogen

1-phenylmethyl-4-piperidone (3612-20-2) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene / 110 °C / Industrial scale 1.2: Raney nickel / 60 °C / 3000.3 Torr / Industrial scale 1.3: 50 °C / Industrial scale 2.1: potassium carbonate / water; tert-butyl alcohol / 45 °C / Industrial scale 2.2: 60 °C / 3000.3 Torr / Industrial scale View Scheme
Multi-step reaction with 2 steps 1: hydrogen; platinum on activated charcoal / 8 h / 80 °C / 3750.38 Torr / Autoclave 2: hydrogen; palladium on activated charcoal / isopropyl alcohol / 7 h / 80 °C / 3750.38 Torr / Autoclave View Scheme
Multi-step reaction with 2 steps 1: sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 3 h / 20 °C 2: palladium on activated charcoal; hydrogen / methanol / 6 h / 20 °C / 3750.38 Torr View Scheme

N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium 10% on activated carbon; hydrogen / methanol 2: trifluoroacetic acid / dichloromethane / 2 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: acetic acid; sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C / Cooling 2: trifluoroacetic acid / dichloromethane / 6 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: acetic acid; sodium tris(acetoxy)borohydride / dichloromethane / 16 h / 0 - 20 °C 2: hydrogenchloride / methanol / 12 h / 40 °C View Scheme
Multi-step reaction with 2 steps 1.1: acetic acid / 1,2-dichloro-ethane / 0.17 h / 20 °C 1.2: 20 °C 2.1: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

4-HYDROXYPIPERIDINE (5382-16-1) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydroxide; water / 1,4-dioxane / 0 - 20 °C 2.1: pyridinium chlorochromate; SiO2 / dichloromethane / 2 h / 20 °C 3.1: acetic acid / 1,2-dichloro-ethane / 0.17 h / 20 °C 3.2: 20 °C 4.1: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

t-butyl 4-hydroxy piperidine-1-carboxylate (109384-19-2) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: pyridinium chlorochromate; SiO2 / dichloromethane / 2 h / 20 °C 2.1: acetic acid / 1,2-dichloro-ethane / 0.17 h / 20 °C 2.2: 20 °C 3.1: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

benzyl 4-oxo-1-piperidinecarboxylate (19099-93-5) → 4-(piperidin-4-yl)morpholine (53617-35-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: titanium(IV) isopropylate 2: hydrogen View Scheme

5-(3-benzofuran-2-yl-phenyl)-1,4-dimethyl-1H-pyrazole-3-carboxylic acid (1107658-97-8) + 4-(piperidin-4-yl)morpholine (53617-35-9) → [5-(3-Benzofuran-2-yl-phenyl)-1,4-dimethyl-1H-pyrazol-3-yl]-(4-morpholin-4-yl-piperidin-1-yl)-methanone (1107656-39-2)

Conditions	Yield
Stage #1: 5-(3-benzofuran-2-yl-phenyl)-1,4-dimethyl-1H-pyrazole-3-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h; Stage #2: 4-(piperidin-4-yl)morpholine With triethylamine In dichloromethane at 0℃; for 3h;	100%

potassium (chloromethyl)trifluoroborate + 4-(piperidin-4-yl)morpholine (53617-35-9) → C10H19BF3N2O(1-)*H(1+)

Conditions	Yield
In tert-Amyl alcohol at 110℃; Inert atmosphere;	100%

trifluoroacetic acid (76-05-1) + 4-(piperidin-4-yl)morpholine (53617-35-9) → 4-piperidin-4-yl-morpholine bis-trifluoroacetate (436099-97-7)

Conditions	Yield
In dichloromethane at 20℃; for 1h;	98%

trifluoro-methane sulfonic acid 9-bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (1256579-48-2) + 4-(piperidin-4-yl)morpholine (53617-35-9) → 6,6-dimethyl-9-bromo-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (1256579-62-0)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 120℃; for 3h;	98%
With N-methylcyclohexylamine at 80 - 90℃; Temperature; Reagent/catalyst; Large scale;	78.6%

1,1-dimethyl-6-ethyl-1,2,3,4-tetrahydro-2-oxo-7-naphthyltriflate + 4-(piperidin-4-yl)morpholine (53617-35-9) → 1,1-dimethyl-6-ethyl-7-[4-(morpholin-4-yl)piperidine-1-yl]-3,4-dihydro-2-naphthalenone

Conditions	Yield
With sodium methylate In 1,4-dioxane at 90℃; for 18h; Solvent; Temperature; Reagent/catalyst;	97%

methyl 3-(bromomethyl)-6-chloro-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1336964-71-6) + 4-(piperidin-4-yl)morpholine (53617-35-9) → methyl 6-chloro-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1336964-72-7)

Conditions	Yield
Stage #1: 4-(piperidin-4-yl)morpholine With potassium carbonate In dichloromethane at 20℃; for 0.5h; Stage #2: methyl 3-(bromomethyl)-6-chloro-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate In dichloromethane at 20℃; for 24h;	96%

5-[(ethoxycarbonyl)methyl]-2-ethylphenyl trifluoromethanesulfonate + 4-(piperidin-4-yl)morpholine (53617-35-9) → 2-{4-ethyl-3-[4-(morpholin-4-yl)piperidin-1-yl]phenyl}acetate

Conditions	Yield
With sodium methylate In N,N-dimethyl-formamide at 100℃; for 12h; Concentration; Temperature; Reagent/catalyst; Solvent; Green chemistry;	96%

4-(8-(bromomethyl)-2-chloro-9-methyl-9H-purin-6-yl)morpholine (1257295-04-7) + 4-(piperidin-4-yl)morpholine (53617-35-9) → 4-(1-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)morpholine (1257296-26-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h;	95%

methyl 3-(bromomethyl)-7-[(2-methylpropyl)oxy]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1336904-99-4) + 4-(piperidin-4-yl)morpholine (53617-35-9) → methyl 7-[(2-methylpropyl)oxy]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1336966-25-6)

Conditions	Yield
With potassium carbonate In acetonitrile for 3h;	95%

formaldehyd (50-00-0) + 2-cyano-6-hydroxybenzothiazole (939-69-5) + 4-(piperidin-4-yl)morpholine (53617-35-9) → 6-hydroxy-7-[[4-(morpholin-4-yl)piperidin-1-yl]methyl]-1,3-benzothiazole-2-carbonitrile

Conditions	Yield
Stage #1: formaldehyd; 4-(piperidin-4-yl)morpholine In acetonitrile at 80℃; for 1h; Stage #2: 2-cyano-6-hydroxybenzothiazole In acetonitrile at 80℃;	95%

5-[2-(ethoxycarbonyl)propan-2-yl]-2-ethylphenyl trifluoromethanesulfonate + 4-(piperidin-4-yl)morpholine (53617-35-9) → ethyl 2-{4-ethyl-3-[4-(morpholine-4-yl)piperidine-1-yl]phenyl}-2-methylpropionate

Conditions	Yield
With sodium t-butanolate In toluene at 90℃; for 18h; Solvent; Temperature; Reagent/catalyst;	95%

7-benzyl-2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine + 4-(piperidin-4-yl)morpholine (53617-35-9) → 4-(1-(7-benzyl-2-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)morpholine

Conditions	Yield
With triethylamine In ethanol at 80℃; for 0.25h; Microwave irradiation; Sealed tube;	95%

4-(2-(2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)ethyl)morpholine + 4-(piperidin-4-yl)morpholine (53617-35-9) → 4-(2-(2-chloro-4-(4-morpholinopiperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)ethyl)morpholine

Conditions	Yield
With triethylamine In ethanol at 80℃; for 0.25h; Microwave irradiation;	95%

1-[4-(2-bromoethyl)phenyl]ethanone (40422-73-9) + 4-(piperidin-4-yl)morpholine (53617-35-9) → 4-acetyl-2-(4-morpholin-4-yl-1-piperidinyl)-1-ethylbenzene

Conditions	Yield
With potassium tert-butylate In dimethyl sulfoxide at 5 - 80℃; Microwave irradiation;	94.9%

4-(2-oxo-1,2,4,5-tetrahydro-benzo[d][1,3]diazepin-3-yl)-piperidine-1-carboxylic acid (R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl ester (866087-24-3) + 4-(piperidin-4-yl)morpholine (53617-35-9) → 2-oxoethyl (1R)-4-(1,2,4,5-tetrahydro-2-oxo-3H-1,3-benzodiazepin-3-yl)-1-[[3,5-dimethyl-4-(phenylmethoxy)phenyl]methyl]-2-[4-(4-morpholinyl)-1-piperidinyl]-1-piperidinecarboxylate

Conditions	Yield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In tetrahydrofuran; ethyl acetate at 0 - 20℃; for 1h;	94%

3-[8-(2,6-difluorophenyl)-2-(methylsulfinyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-(1-methylethyl)benzamide (911693-62-4) + 4-(piperidin-4-yl)morpholine (53617-35-9) → 3-{8-(2,6-difluorophenyl)-2-[4-(4-morpholinyl)-1-piperidinyl]-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl}-4-methyl-N-(1-methylethyl)benzamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran; chloroform at 20℃;	94%
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran; chloroform at 20℃;	94%

1,1-dimethyl-3,4-dihydro-6-ethyl-7-bromonaphthalen-2-one + 4-(piperidin-4-yl)morpholine (53617-35-9) → 1,1-dimethyl-6-ethyl-7-[4-(morpholin-4-yl)piperidine-1-yl]-3,4-dihydro-2-naphthalenone

Conditions	Yield
With sodium methylate In N,N-dimethyl-formamide at 100℃; for 8h; Reagent/catalyst; Solvent; Temperature;	92.3%

1-bromomethyl-4-bromobenzene (589-15-1) + 4-(piperidin-4-yl)morpholine (53617-35-9) → 4-(1-(4-bromobenzyl)piperidin-4-yl)morpholine (496775-18-9)

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 44h;	92%

9-ethyl-8-iodo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]-carbazole-3-carbonitrile + 4-(piperidin-4-yl)morpholine (53617-35-9) → CH5424802 (1256580-46-7)

Conditions	Yield
With sodium methylate In N,N-dimethyl-formamide at 100℃; for 12h; Reagent/catalyst; Temperature;	92%
With sodium methylate In toluene at 100℃; for 10h; Reagent/catalyst; Solvent;	89%
With potassium tert-butylate; L-proline In 1,4-dioxane at 120℃; for 24h; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;	10.3 g

6-((3-fluorobenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxylic acid + 4-(piperidin-4-yl)morpholine (53617-35-9) → (6-((3-fluorobenzyl)amino)imidazo[1,2-b]pyridazin-3-yl)(4-morpholinopiperidin-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 60℃; for 1h;	91.39%

tert-butyl 4-(4-ethyl-3-iodo-phenyl)-4-methyl-3-oxo-pentanoate + 4-(piperidin-4-yl)morpholine (53617-35-9) → tert-butyl 4-{4-ethyl-3-[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-4-methyl-3-oxopentanoate

Conditions	Yield
With sodium ethanolate In toluene at 110℃; for 6h; Reagent/catalyst; Solvent; Temperature;	91%
With iron(III)-acetylacetonate; caesium carbonate; copper(II) oxide In N,N-dimethyl-formamide at 90℃; for 20h; Reagent/catalyst; Solvent; Temperature; Sealed tube; Inert atmosphere; Green chemistry;	82%

6-ethyl-1,2,3,4-tetrahydro-2-oxo-7-naphthalyl trifluoromethanesulfonate + 4-(piperidin-4-yl)morpholine (53617-35-9) → 6-ethyl-7-[4-(morpholin-4-yl)piperidin-1-yl]-3,4-dihydro-2-naphthalenone

Conditions	Yield
With sodium methylate In N,N-dimethyl-formamide at 100℃; for 8h; Solvent; Temperature; Reagent/catalyst;	91%

methyl 3-(bromomethyl)-6-(trifluoromethyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1336965-10-6) + 4-(piperidin-4-yl)morpholine (53617-35-9) → methyl 3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-6-(trifluoromethyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1336965-12-8)

Conditions	Yield
With potassium carbonate In acetonitrile for 5h; Reflux;	90%

methyl 3-(bromomethyl)-6-chloro-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1336965-98-0) + 4-(piperidin-4-yl)morpholine (53617-35-9) → methyl 6-chloro-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1336965-99-1)

Conditions	Yield
In acetonitrile at 20℃; for 3h;	90%

6-ethyl-7-bromo-3,4-dihydro-2-naphthalenone + 4-(piperidin-4-yl)morpholine (53617-35-9) → 6-ethyl-7-[4-(morpholin-4-yl)piperidin-1-yl]-3,4-dihydro-2-naphthalenone

Conditions	Yield
With sodium isopropylate In 1,4-dioxane at 90℃; for 12h; Temperature; Reagent/catalyst; Solvent;	90%

(Z)-5-(3-phenoxybenzylidene)-2-(methylthio)-3H-imidazol-4(5H)-one + 4-(piperidin-4-yl)morpholine (53617-35-9) → (Z)-5-(3-phenoxybenzylidene)-2-(4-morpholinopiperidin-1-yl)imidazol-4(5H)-one hydrochloride

Conditions	Yield
Stage #1: (Z)-5-(3-phenoxybenzylidene)-2-(methylthio)-3H-imidazol-4(5H)-one; 4-(piperidin-4-yl)morpholine at 120 - 130℃; for 0.25h; Stage #2: In ethanol Reflux; Stage #3: With hydrogenchloride	89.26%

1-bromo-3-{[(4-methoxybenzyl)oxy]methyl}benzene (1274038-52-6) + 4-(piperidin-4-yl)morpholine (53617-35-9) → 4-[1-(3-{[(4-methoxybenzyl)oxy]methyl}phenyl)piperidin-4-yl]morpholine

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 100℃; for 1h; Buchwald-Hartwig Coupling; Inert atmosphere;	89%

methyl 3-(bromomethyl)-6-(ethylsulfonyl)-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1335116-56-7) + 4-(piperidin-4-yl)morpholine (53617-35-9) → methyl 6-(ethylsulfonyl)-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1335116-59-0)

Conditions	Yield
In acetonitrile at 20℃; for 3h;	87%

Upstream product

• 110-91-8 morpholine 
• 67-63-0 isopropyl alcohol 
• 29976-53-2 N-ethoxycarbonyl-4-piperidone 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 3612-20-2 1-phenylmethyl-4-piperidone 
• 19099-93-5 benzyl 4-oxo-1-piperidinecarboxylate 
• 109384-19-2 t-butyl 4-hydroxy piperidine-1-carboxylate 
• 5382-16-1 4-HYDROXYPIPERIDINE 
• 125541-20-0 tert-butyl 4-(morpholin-4-yl)piperidine-1-carboxylate 
• 334942-09-5 benzyl 4-morpholin-4-ylpiperidine-1-carboxylate 
• 186650-77-1 4-(4-morpholinopiperidin-1-yl)benzonitrile 
• 415967-79-2 4-(1-benzyl-piperidin-4-yl)-morpholine 
• 2767-91-1 4-morpholinopyridine 

Downstream Products

• 345235-10-1 3-(4-morpholin-4-yl-piperidin-1-ylmethyl)-2-phenyl-quinoline-4-carboxylic acid methyl ester 
• 1151934-75-6 1-(adamantan-1-yl)-3-[3-[4-[(4-morpholinyl)piperidinyl]carbonyl]phenyl]urea 
• 1198229-85-4 5-(8-trifluoromethyl-4-(4-morpholinopiperidin-1-yl)quinolin-3-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol 
• 1026498-25-8 C₂₇H₃₀F₃N₅O₄ 
• 1464151-71-0 4-(6-(4-(4-morpholinopiperidine-1-carbonyl)phenyl)imidazo[1,2-a]pyridin-3-yl)benzonitrile 
• 1464155-59-6 (4-(3-bromoimidazo[1,2-b]pyridazin-6-yl)phenyl)(4-morpholinopiperidine-1-yl)methanone 
• 1279027-10-9 tert-butyl [2-(methyl-{3-[2-(4-morpholin-4-ylpiperidin-1-yl)pyrimidin-5-yl]benzyl}amino)-2-oxoethyl]carbamate 
• 1383744-41-9 C₂₅H₃₁F₂N₇O₃S 

Relevant articles and documents

METHOD FOR PREPARING 4-(PIPERIDIN-4-YL)MORPHOLINE

The object of the present invention is to provide a method for preparing 4-(piperidin-4-yl)morpholine, which is easy to operate. The object can be solved by a method for preparing 4-(1-benzylpiperidin-4-yl)morpholine, characterized in that 5-fold molar or more of morpholine is added to 1-benzyl-4-piperidone, and the mixture is reacted with hydrogen under 1 MPa or less in the presence of platinum catalyst or palladium catalyst.

2-amino-4-substituted pyridine derivative as well as synthesis method and application thereof

The invention discloses a 2-amino-4-substituted pyridine derivative as well as a synthesis method and an application thereof. The derivative with the structural formula is a compound with the structure or pharmacologically acceptable salt, hydrate, solvate, polymorphic substance, tautomer, stereoisomer, isotope derivative or prodrug of the compound. The 2-amino-4-substituted pyridine derivative has higher EGFR (epidermal growth factor receptor) inhibition activity, has higher inhibition activity for human epidermal cell carcinoma cells, glioblastoma cells and the like and can be used for preparing drugs for treating and/or preventing and/or delaying and/or assisting in treatment and/or treatment of diseases related with too high EGFR activity.

C-3 NOVEL TRITERPENONE WITH C-17 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS

The present invention relates to C-3 novel triterpenone with C-17 reverse amide compounds of Formula (I); and pharmaceutically acceptable salts thereof, wherein ring Formula (II), R1, R2, R3, R4, R5, R6, R7, 'n' and 'm' are as defined in Formula (I). The invention also relates to C-3 novel triterpenone with C-17 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.

CYCLIC AMINE DERIVATIVE AND PHARMACEUTICAL USE THEREOF

A compound exerts a strong analgesic effect against pain, in particular, neuropathic pain and/or fibromyalgia syndrome. A cyclic amine derivative represented by general formula or a pharmacologically acceptable salt thereof A method of treating neuropathic pain includes administering a therapeutically effective amount of the cyclic amine derivative to a mammal. A method of treating fibromyalgia syndrome includes administering a therapeutically effective amount of the cyclic amine derivative to a mammal.

Tyrosine Kinase Inhibitor And Uses Thereof

Disclosed is a compound of Formula (I) or a pharmaceutically acceptable salt, ester, or solvate thereof, or their stereoisomers, which can be used as tyrosine kinase inhibitor. Also disclosed is a method for preparing the compound, a pharmaceutical composition and a kit comprising the compound, and uses of the compound. The compound can be used as tyrosine kinase inhibitor, or can be used to reduce or inhibit activity of EGFR or mutant thereof, such as EGFR mutant comprising T790M mutation, in a cell, or to treat and/or prevent a disease associated with overactivity of EGFR, such as cancer.

CYCLIC AMINE DERIVATIVE AND PHARMACEUTICAL USE THEREOF

A compound exerts a strong analgesic effect against pain, in particular, neuropathic pain and/or fibromyalgia syndrome. The cyclic amine derivative is represented by formula, a prodrug thereof or a pharmacologically acceptable salt thereof: wherein A represents a group represented by Formula (IIa), (IIb) or (IIc): wherein R3 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, R4 represents a hydrogen atom or an alkylcarbonyl group having 2 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms and optionally substituted with an alkylcarbonylamino group having 2 to 6 carbon atoms and n represents 1 or 2, in which when R3 and R4 each independently represent an alkyl group having 1 to 6 carbon atoms, R1 represents an alkyl group having 1 to 6 carbon atoms and substituted with a hydroxyl group, an amino group or a carboxyl group.

4-morpholino process for preparation of piperidines (by machine translation)

The invention relates to a method for preparing pharmaceutical intermediates, in particular to a 4? Morpholino process for preparation of piperidines. The invention will create 1? Benzyltin? 4? Piperidone and morpholine reaction is carried out by preparing 4? (1? Benzyl piperidine? 4? Yl) morpholine b hydrochloric acid, then to continue reaction produce the final product is 4? Morpholino piperidine. Creation method of this invention is simple and convenient, high yield and purity of the product, mild reaction conditions the safety is high, is particularly suitable for industrial production. (by machine translation)

Cyclic amine derivative and pharmaceutical use thereof

The purpose of the present invention is to provide a compound that exerts a strong analgesic action against on pain, in particular, against neuropathic pain and/or fibromyalgia syndrome. The present invention provides a cyclic amine derivative represented by chemical formula, a prodrug thereof or a pharmaceutically acceptable salt thereof.

Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists

Melanin concentrating hormone (MCH) is an important mediator of energy homeostasis and plays a role in metabolic and CNS disorders. The modeling-supported design, synthesis and multi-parameter optimization (biological activity, solubility, metabolic stability, hERG) of novel quinazoline derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified. Clusters of refined hMCHR1 homology models derived from the X-ray structure of the β2-adrenergic receptor, including extracellular loops, were developed and used to guide the design.

NOVEL PREPARATION PROCESS

A process for preparing compounds of the formula (I) in which R1 and R2 are as defined in the description.