314268-40-1

Basic information

• Product Name: METHYL 4-[(4-METHYLPIPERAZIN-1-YL)METHYL]BENZOATE
• Synonyms: METHYL 4-[(4-METHYLPIPERAZIN-1-YL)METHYL]BENZOATE;METHYL 4-[(4-METHYL-1-PIPERAZINYL)METHYL]BENZOATE;BENZOIC ACID, 4-[(4-METHYL-1-PIPERAZINYL)METHYL]-METHYL ESTER;Methyl 4-[(4-methylpiperazin-1-yl)methyl]benzoate 97%;Methyl 4-(4-Methylpiperazinomethyl)benzoate
• CAS NO: 314268-40-1
• Molecular Formula: C₁₄H₂₀N₂O₂
• Molecular Weight: 248.32
• Mol File: 314268-40-1.mol
• Article Data: 33

Chemical Properties

• Melting Point: 148-150 °C
• Boiling Point: 351.9 °C at 760 mmHg
• Flash Point: 166.6 °C
• Appearance: /
• Density: 1.104 g/cm³
• Vapor Pressure: 3.97E-05mmHg at 25°C
• Refractive Index: 1.546
• PKA: 7.55±0.10(Predicted)
• CAS DataBase Reference: METHYL 4-[(4-METHYLPIPERAZIN-1-YL)METHYL]BENZOATE(CAS DataBase Reference)
• NIST Chemistry Reference: METHYL 4-[(4-METHYLPIPERAZIN-1-YL)METHYL]BENZOATE(314268-40-1)
• EPA Substance Registry System: METHYL 4-[(4-METHYLPIPERAZIN-1-YL)METHYL]BENZOATE(314268-40-1)

Safety Data

• Hazard Codes: C
• Hazardous Substances Data: 314268-40-1(Hazardous Substances Data)

Usage

General Description

METHYL 4-[(4-METHYLPIPERAZIN-1-YL)METHYL]BENZOATE is a chemical compound that belongs to the class of benzoate esters. It consists of a benzoate group and a methyl group attached to a piperazine ring, which is a common structural motif in pharmaceuticals and bioactive compounds. METHYL 4-[(4-METHYLPIPERAZIN-1-YL)METHYL]BENZOATE has potential applications in the field of medicinal chemistry due to the presence of the piperazine moiety, which is often associated with central nervous system activity. Additionally, the benzoate ester group may contribute to the compound's solubility and stability, making it suitable for formulation in pharmaceutical products. Overall, METHYL 4-[(4-METHYLPIPERAZIN-1-YL)METHYL]BENZOATE has properties that make it relevant for further studies and potential use in drug development.

InChI:InChI=1/C14H20N2O2/c1-15-7-9-16(10-8-15)11-12-3-5-13(6-4-12)14(17)18-2/h3-6H,7-11H2,1-2H3

Synthetic route

1-methyl-piperazine (109-01-3) + methyl 4-formylbenzoate (1571-08-0) → 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1)

Conditions	Yield
With sodium tetrahydroborate; acetic acid In chloroform at 0 - 20℃; for 13h;	99%
With sodium tetrahydroborate; acetic acid In chloroform at 0 - 20℃;	98%
With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 1.5h;	98%

1-methyl-piperazine (109-01-3) + Methyl 4-(bromomethyl)benzoate (2417-72-3) → 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1)

Conditions	Yield
In tetrahydrofuran at 100℃; Cooling with ice; Microwave irradiation;	97%
With potassium carbonate In acetonitrile at 20℃; for 7h;	93%
With triethylamine In dichloromethane at 20℃;	93%

methanol (67-56-1) + 4-(4-methylpiperazin-1-ylmethyl)benzoic acid (106261-48-7) → 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1)

Conditions	Yield
With toluene-4-sulfonic acid for 48h; Heating;	85%

1-methyl-4-((trifluoro-λ4-boranyl)methyl)piperazine potassium (1015484-22-6) + 4-methoxycarbonylphenyl bromide (619-42-1) → 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1)

Conditions	Yield
With C52H67ClFeNPPd; caesium carbonate In tetrahydrofuran; water at 80℃; for 12h; Suzuki-Miyaura cross-coupling;	83%

1-methyl-piperazine (109-01-3) + methyl 4-formylbenzoate (1571-08-0) → 1-formyl-4-methylpiperidine (7556-55-0) + 4-(methoxycarbonyl)benzyl alcohol (6908-41-4) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1)

Conditions	Yield
Stage #1: 1-methyl-piperazine With formic acid for 0.25h; cooling; Stage #2: methyl 4-formylbenzoate at 180 - 200℃; for 8h; Leuckart-Wallach reaction; Further stages.;	A n/a B n/a C 70%

4-(4-methylpiperazin-1-ylmethyl)benzoic acid (106261-48-7) + diazomethyl-trimethyl-silane (18107-18-1) → 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1)

Conditions	Yield
In methanol; diethyl ether; toluene at 20℃; for 21.1667h;	44.2%

1-methyl-piperazine (109-01-3) + p-methyloxycarbonylbenzyl chloride (34040-64-7) → 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1)

Conditions	Yield
With sodium iodide In acetone at 60℃; for 10.5h;

4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → 4-(4-methylpiperazin-1-ylmethyl)benzoic acid (106261-48-7)

Conditions	Yield
With water; lithium hydroxide In tetrahydrofuran for 4h; Reflux;	100%
With water; lithium hydroxide In tetrahydrofuran for 4h; Reflux;	100%

4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → 4-((4-methylpiperazin-1-yl)methyl)benzoic acid dihydrochloride

Conditions	Yield
With hydrogenchloride In water at 100℃; for 3h;	98%
With hydrogenchloride In water Reflux;	96%
With hydrogenchloride; water for 10h; Reflux;	286 mg

6-methyl-N-phenylbenzene-1,3-diamine (41131-23-1) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-(4-methyl-3-(phenylamino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide

Conditions	Yield
With [m-(1,4-diazabicyclo[2.2.2]octanekN1:kN4)]hexamethyldialuminum In toluene for 1h; Schlenk technique; Reflux;	98%

N,N-(4-methyl-3-aminophenyl)[4-(pyridin-3-yl)-pyrimidin-2-yl]amine (571187-03-6) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → imatinib (152459-95-5)

Conditions	Yield
With sodium methylate In tetrahydrofuran; methanol Product distribution / selectivity; Reflux;	91%

6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → imatinib (152459-95-5)

Conditions	Yield
With sodium methylate In tetrahydrofuran at 70℃;	91%
With trimethylaluminum In toluene at 40℃; for 0.5h; Inert atmosphere;

4-(5-bromo-2-thienyl)-1,3-thiazol-2-amine (34801-14-4) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-(4-(5-bromothiophen-2-yl)thiazol-2-yl)-4-((4-methylpiperazin-1-yl)methyl)benzamide

Conditions	Yield
Stage #1: 4-(5-bromothiophen-2-yl)thiazol-2-amine With trimethylaluminum In n-heptane; toluene at 50℃; for 0.333333h; Inert atmosphere; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In n-heptane; toluene Reflux;	91%

4-(4-bromophenyl)-1,3-thiazol-2-amine (2103-94-8) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-(4-(3-bromophenyl)thiazol-2-yl)-4-((4-methylpiperazin-1-yl)methyl)benzamide

Conditions	Yield
Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine With trimethylaluminum In n-heptane; toluene at 50℃; for 0.333333h; Inert atmosphere; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In n-heptane; toluene Reflux;	86%

N1-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]-6-methyl-1,3-phenylenediamine (660837-08-1) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → masitinib (790299-79-5)

Conditions	Yield
Stage #1: N1-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]-6-methyl-1,3-phenylenediamine With trimethylaluminum In hexane; dichloromethane at 5 - 15℃; for 2h; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In hexane; dichloromethane at 20℃; for 21.1667h; Heating / reflux; Stage #3: With sodium hydroxide; water In hexane; dichloromethane at 20℃; for 3h; Product distribution / selectivity;	78%
Stage #1: N1-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]-6-methyl-1,3-phenylenediamine With trimethylaluminum In dichloromethane; toluene at 0 - 20℃; for 0.5h; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In dichloromethane; toluene for 5h; Heating / reflux;	72%
Stage #1: N1-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]-6-methyl-1,3-phenylenediamine With trimethylaluminum In dichloromethane; toluene at 0 - 20℃; for 0.5h; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In dichloromethane; toluene for 5h; Heating / reflux;	72%

4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → (4-((4-methylpiperazin-1-yl)methyl)phenyl)methanol (622381-65-1)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; Cooling with ice;	77%
Stage #1: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; Stage #2: With sodium hydroxide; water In tetrahydrofuran	73%
With lithium aluminium tetrahydride In tetrahydrofuran Reduction;
With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 1.5h; Inert atmosphere;

aniline (62-53-3) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → 4-(4-methylpiperazinomethyl) N-phenylbenzamide

Conditions	Yield
With sodium methylate In toluene for 6h; Heating;	75%

4-methylbenzene-1,3-diamine (95-80-7) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-(3-amino-4-methylphenyl)-4-((4-methyl-1-piperazinyl)methyl)benzamide

Conditions	Yield
With aluminum (III) chloride In toluene; acetonitrile at 40℃; for 8.5h; Inert atmosphere;	75%

cyclohexylamine (108-91-8) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → 4-(4-methylpiperazinomethyl) N-cyclohexylbenzamide

Conditions	Yield
With sodium ethanolate In toluene for 6h; Heating;	70%

3-bromo-4-methylaniline (7745-91-7) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-(3-bromo-4-methylphenyl)-4-((4-methylpiperazin-1-yl)-methyl)benzamide (581076-59-7)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 20℃; for 17h; Inert atmosphere;	65%
With trimethylaluminum In toluene at 40℃; for 1h; Inert atmosphere;	4.69 g

4-(4-bromo-3-chlorophenyl)thiazol-2-amine + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-(4-(4-bromo-3-chlorophenyl)thiazol-2-yl)-4-((4-methylpiperazin-1-yl)methyl)benzamide

Conditions	Yield
Stage #1: 4-(4-bromo-3-chlorophenyl)thiazol-2-amine With trimethylaluminum In n-heptane; toluene at 50℃; for 0.333333h; Inert atmosphere; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In n-heptane; toluene Reflux;	64%

4-(3-bromo-4-methylphenyl)thiazol-2-amine + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-(4-(3-bromo-4-methylphenyl)thiazol-2-yl)-4-((4-methylpiperazin-1-yl)methyl)benzamide

Conditions	Yield
Stage #1: 4-(3-bromo-4-methylphenyl)thiazol-2-amine With trimethylaluminum In n-heptane; toluene at 50℃; for 0.333333h; Inert atmosphere; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In n-heptane; toluene Reflux;	60%

4-(4-bromo-3-methylphenyl)thiazol-2-amine + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-(4-(4-bromo-3-methylphenyl)thiazol-2-yl)-4-((4-methylpiperazin-1-yl)methyl)benzamide

Conditions	Yield
Stage #1: 4-(4-bromo-3-methylphenyl)thiazol-2-amine With trimethylaluminum In n-heptane; toluene at 50℃; for 0.333333h; Inert atmosphere; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In n-heptane; toluene Reflux;	59%

4-(4-bromophenyl)-1,3-thiazol-2-amine (2103-94-8) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-(4-(4-bromophenyl)thiazol-2-yl)-4-((4-methylpiperazin-1-yl)methyl)benzamide

Conditions	Yield
Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine With trimethylaluminum In toluene at 50℃; for 0.333333h; Inert atmosphere; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In toluene Reflux;	48%

tert-butyl 5-amino-3-(3,5-dimethoxyphenethyl)-1H-pyrazole-1-carboxylate (1035270-66-6) + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(4-methylpiperazin-1-yl)methyl]benzamide (1035269-80-7)

Conditions	Yield
Stage #1: tert-butyl 5-amino-3-(3,5-dimethoxyphenethyl)-1H-pyrazole-1-carboxylate; 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester With sodium hexamethyldisilazane In tetrahydrofuran for 0.166667h; Stage #2: With sodium hexamethyldisilazane In tetrahydrofuran; N,N-dimethyl acetamide at 20℃; for 61.5h;	5.19%

4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → 2,2-dimethyl-propionic acid 4-(4-methyl-piperazin-1-ylmethyl)-benzyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: LiAlH4 / tetrahydrofuran 2: DCCD; DMAP; pyridine / CH2Cl2 View Scheme

4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → 3,4-dimethoxy-benzoic acid 4-(4-methyl-piperazin-1-ylmethyl)-benzyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: LiAlH4 / tetrahydrofuran 2: DCCD; DMAP; pyridine / CH2Cl2 View Scheme

4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → 4-(4-methylpiperazin-1-ylmethyl)benzoic acid methyl ester hydrochloride (728936-43-4)

Conditions	Yield
With hydrogenchloride In diethyl ether; ethyl acetate for 1h;

6-[2-(4-fluorophenyl)chroman-6-yloxy]-pyridin-3-ylamine + 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → N-{6-[2-(4-fluorophenyl)chroman-6-yloxy]-pyridin-3-yl}-4-(4-methyl-piperazin-1-ylmethyl)benzamide

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 7h;

4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester (314268-40-1) → C13H20N4O (1236355-89-7)

Conditions	Yield
With hydrazine hydrate In ethanol for 1h; Reflux;

Upstream product

• 109-01-3 1-methyl-piperazine 
• 2417-72-3 Methyl 4-(bromomethyl)benzoate 
• 67-56-1 methanol 
• 106261-48-7 4-(4-methylpiperazin-1-ylmethyl)benzoic acid 
• 34040-64-7 p-methyloxycarbonylbenzyl chloride 
• 1571-08-0 methyl 4-formylbenzoate 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 1015484-22-6 1-methyl-4-((trifluoro-λ⁴-boranyl)methyl)piperazine potassium 
• 619-42-1 4-methoxycarbonylphenyl bromide 

Downstream Products

• 622381-65-1 (4-(4-methyl piperazin-1-ylmethyl)phenyl)-methanol 
• 106261-48-7 4-(4-methylpiperazin-1-ylmethyl)benzoic acid 
• 728936-43-4 4-(4-methylpiperazin-1-ylmethyl)benzoic acid methyl ester hydrochloride 
• 1035269-80-7 N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(4-methylpiperazin-1-yl)methyl]benzamide 
• 790299-79-5 masitinib 
• 1236355-89-7 C₁₃H₂₀N₄O 
• 1262215-41-7 N-(3-fluoro-4-methyl-5-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide 
• 152459-95-5 imatinib 
• 1616628-84-2 N-(2-acetyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-methyl-5-[4-(4-methylpiperazin-1-ylmethyl)-benzoylamino]-benzamide 
• 1240322-41-1 ND₀₁₁₈ 
• 1616628-87-5 5-{(2-methyl-5-[4-((4-methylpiperazin-1-yl)methyl)benzoylamino]benzyl)amino}-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid 
• 581076-63-3 N-(3-amino-4-methylphenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide 
• 1616689-28-1 5-{(2-methyl-5-[4-((4-methylpiperazin-1-yl)methyl)benzoylamino]phenoxy)methyl}-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid methyl ester 
• 1616689-18-9 5-(2-{2-methyl-5-[4-(4-methylpiperazin-1-ylmethyl)-benzoylamino]-phenyl}-vinyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid methyl ester 

Relevant articles and documents

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N-phenyl-2-pyrimidine-amine derivatives

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