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
• Article Data: 17

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

Reactant for synthesis of:Selective adenosine A2A receptor antagonistsAntidepressentsSmall molecules that restore E-cadherin expression and reduce invasion in colorectal carcinoma cellsOrally bioavailable P2Y12 antagonists for inhibition of platelet aggregationQuinoline derivatives with antimicrobial activityAntimalarials

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

• 2767-91-1 4-morpholinopyridine 
• 110-91-8 morpholine 
• 3612-20-2 1-phenylmethyl-4-piperidone 
• 19099-93-5 benzyl 4-oxo-1-piperidinecarboxylate 
• 5382-16-1 4-HYDROXYPIPERIDINE 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 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 
• 67-63-0 isopropyl alcohol 
• 29976-53-2 N-ethoxycarbonyl-4-piperidone 
• 109384-19-2 t-butyl 4-hydroxy piperidine-1-carboxylate 

Downstream Products

• 345235-10-1 3-(4-morpholin-4-yl-piperidin-1-ylmethyl)-2-phenyl-quinoline-4-carboxylic acid methyl ester 
• 1003933-11-6 1-(benzyloxy)-4-[4-(4-morpholinyl)-1-piperidinyl]-1,8-naphthyridin-2(1H)-one 
• 845795-73-5 (4-Methanesulfonyl-phenyl)-[2-(4-morpholin-4-yl-piperidin-1-yl)-9-(tetrahydro-pyran-2-yl)-9H-purin-6-yl]-amine 
• 288252-22-2 5-amino-2-(4-morpholinopiperidin-1-yl)benzonitrile 
• 666851-66-7 C₃₅H₄₈N₄O₂S 
• 1107656-39-2 [5-(3-Benzofuran-2-yl-phenyl)-1,4-dimethyl-1H-pyrazol-3-yl]-(4-morpholin-4-yl-piperidin-1-yl)-methanone 
• 1198229-85-4 5-(8-trifluoromethyl-4-(4-morpholinopiperidin-1-yl)quinolin-3-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol 
• 866086-05-7 4-(2-oxo-1,2,4,5-tetrahydro-benzo[d][1,3]diazepin-3-yl)-piperidine-1-carboxylic acid (R)-1-(4-hydroxy-3,5-dimethyl-phenyl)-2-(4-morpholin-4-yl-piperidin-1-yl)-2-oxo-ethyl ester 
• 1026498-25-8 C₂₇H₃₀F₃N₅O₄ 
• 1033594-29-4 {2-[4-(3-fluoro-phenyl)-6-(4-morpholin-4-yl-piperidin-1-yl)-[1,3,5]triazin-2-yl]-1,2,3,4-tetrahydro-isoquinolin-(3R)-yl}-methanol 

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.

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.