2498-50-2

Basic information

• Product Name: 4-Aminobenzamidine dihydrochloride
• Synonyms: 4-AMINOBENZAMIDINE DIHYDROCHLORIDE;4-AMINOBENZAMIDINE HCL SALT;BENZENECARBOXIMIDAMIDE, 4-AMINO-, DIHYDROCHLORIDE;P-AMINOBENZAMIDINE DIHCL;P-AMINOBENZAMIDINE DIHYDROCHLORIDE;4-amino-benzenecarboximidamiddihydrochloride;4-aminobenzenecarboximidamidedihydrochloride;p-amino-benzamidindihydrochloride
• CAS NO: 2498-50-2
• Molecular Formula: C₇H₉N₃*2ClH
• Molecular Weight: 208.09
• EINECS: 219-692-2
• Product Categories: Anilines, Aromatic Amines and Nitro Compounds;Amines;Miscellaneous;Broad Spectrum Inhibitors of Proteolytic Enzyme Classes;Other Fluorescent LabelsEnzyme Inhibitors;Protease InhibitorsFluorescent Stains;Protein Stains;Protein Stains For SpectroscopyProtease Inhibitors;Serine Protease Inhibitors;Fluorescent Labels;Fluorescent Probes, Labels, Particles and Stains;Protease Inhibitors;Imines/AmidinesFluorescent Probes, Labels, Particles and Stains;Nitrogen Compounds;Organic Building Blocks;Other Fluorescent Labels;inhibitor
• Mol File: 2498-50-2.mol
• Article Data: 9

Chemical Properties

• Melting Point: >300 °C(lit.)
• Boiling Point: 289.8 °C at 760 mmHg
• Flash Point: 129 °C
• Appearance: White to yellow/Fine Crystalline Powder
• Density: 1.26g/cm3
• Vapor Pressure: 0.00216mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Water
• Sensitive: Hygroscopic
• Stability: Hygroscopic
• BRN: 3692927
• CAS DataBase Reference: 4-Aminobenzamidine dihydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Aminobenzamidine dihydrochloride(2498-50-2)
• EPA Substance Registry System: 4-Aminobenzamidine dihydrochloride(2498-50-2)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-22
• Safety Statements: 26-37/39-36
• WGK Germany: 3
• RTECS: CV6126500
• F: 3-10-21
• Hazardous Substances Data: 2498-50-2(Hazardous Substances Data)

Usage

Chemical Properties

white to yellowish fine crystalline powder

Uses

4-Aminobenzamidine dihydrochloride is a synthetic diamidine derivative that acts as a urokinase inhibitor as well as trypsin inhibitor. It is used as a ligand in affinity chromatography for purification and immobilization of enzymes.

Application

4-Aminobenzamidine dihydrochloride can be used to synthesize:Orally active fibrinogen receptor antagonists based on benzamidines.Benzamidine derivatives that are selective and potent serine protease inhibitors.Novel pyrrolo [3,2-c] quinolines that are structural analogs of topoisomerase inhibitors such as coralyne and fagaronine.Synthesis of a selective inhibitor of PRMT1 (SKLB-639)

Preparation

4-Aminobenzamididine dihydrochloride is obtained by cyanation, addition, amination and reduction of 4-nitrobenzoic acid.

InChI:InChI=1/C7H9N3/c8-6-3-1-5(2-4-6)7(9)10/h1-4H,8H2,(H3,9,10)/p+1

Synthetic route

N-(4-cyanophenyl)acetamide (35704-19-9) → 4-aminobenzamidine dihydrochloride (2498-50-2)

Conditions	Yield
Stage #1: N-(4-cyanophenyl)acetamide With sodium amide In dimethyl sulfoxide at 20 - 80℃; for 1.5h; Large scale; Stage #2: With hydrogenchloride In ethanol; dimethyl sulfoxide at 0℃; for 1.5h; pH=3 - 4; Solvent; Reagent/catalyst; Temperature; Large scale;	97.8%

4-nitrobenzamidine (25412-75-3) → 4-aminobenzamidine dihydrochloride (2498-50-2)

Conditions	Yield
Stage #1: 4-nitrobenzamidine With iron; acetic acid In ethanol; water at 60 - 80℃; for 4h; Stage #2: With hydrogenchloride In ethanol; water Reagent/catalyst;	94.7%

4-Aminobenzonitrile (873-74-5) → 4-aminobenzamidine dihydrochloride (2498-50-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogenchloride / 16 h / -10 - 40 °C / Inert atmosphere 2.1: ammonia / ethanol / 2 h / 20 - 40 °C / Inert atmosphere 2.2: 0.5 h / 60 - 70 °C View Scheme
Multi-step reaction with 2 steps 1.1: hydrogenchloride / -10 - 40 °C / Inert atmosphere 2.1: ammonia / ethanol / 2 h / 20 - 40 °C / Inert atmosphere 2.2: 0.5 h / 60 - 70 °C View Scheme

C8H10N2O*2ClH → 4-aminobenzamidine dihydrochloride (2498-50-2)

Conditions	Yield
Stage #1: C8H10N2O*2ClH With ammonia In ethanol at 20 - 40℃; for 2h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol; water at 60 - 70℃; for 0.5h; Concentration; Solvent; Temperature;	18.3 g
Stage #1: C8H10N2O*2ClH With ammonia In ethanol at 20 - 40℃; for 2h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol; water at 60 - 70℃; for 0.5h; Concentration;	18.3 g

ethyl 4-aminobenzimidate dihydrochloride → 4-aminobenzamidine dihydrochloride (2498-50-2)

Conditions	Yield
Stage #1: ethyl 4-aminobenzimidate dihydrochloride With ammonia In ethanol at 20 - 40℃; for 2h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol; water at 60 - 70℃; for 0.5h; Concentration; Solvent; Temperature;	22.6 g
Stage #1: ethyl 4-aminobenzimidate dihydrochloride With ammonia In ethanol at 20 - 40℃; for 2h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol; water at 60 - 70℃; for 0.5h;	22.6 g

4-nitrobenzonitrile (619-72-7) → 4-aminobenzamidine dihydrochloride (2498-50-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / 20 h / 20 °C / Inert atmosphere 2: ammonium carbonate / ethanol / 20 h / 20 °C / Inert atmosphere 3: acetic acid; iron / ethanol; water / 4 h / 60 - 80 °C View Scheme
Multi-step reaction with 3 steps 1: thionyl chloride / 24 h / 20 °C / Inert atmosphere 2: ammonium carbonate / methanol / 16 h / 20 °C / Inert atmosphere 3: acetic acid; iron / ethanol; water / 4 h / 60 - 80 °C View Scheme

4-nitrobenzimidic acid methyl ester (52708-02-8) → 4-aminobenzamidine dihydrochloride (2498-50-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonium carbonate / methanol / 16 h / 20 °C / Inert atmosphere 2: acetic acid; iron / ethanol; water / 4 h / 60 - 80 °C View Scheme

methanol (67-56-1) + [(p-methylphenyl)sulfonylmethyl]isonitrile (38622-91-2, 36635-61-7) + 4-isopropoxy-5-ethoxy-benzaldehyde (284044-35-5) + 4-aminobenzamidine dihydrochloride (2498-50-2) → (4-Carbamimidoylphenylamino)-(3-ethoxy-4-isopropoxyphenyl)acetic acid methyl ester (883574-18-3)

Conditions	Yield
Stage #1: 4-isopropoxy-5-ethoxy-benzaldehyde; 4-aminobenzamidine dihydrochloride In methanol at 60℃; for 0.5h; Stage #2: methanol; [(p-methylphenyl)sulfonylmethyl]isonitrile; boron trifluoride diethyl etherate at 0 - 20℃; Stage #3: With ammonia; water In ethyl acetate	100%

n-hexyl chloroformate (6092-54-2) + 4-aminobenzamidine dihydrochloride (2498-50-2) → 4-aminobenzamidine-N-hexylcarbamate hydrochloride (1307233-93-7)

Conditions	Yield
Stage #1: n-hexyl chloroformate; 4-aminobenzamidine dihydrochloride With sodium hydroxide In acetone at 5 - 20℃; for 0.25h; Stage #2: With hydrogenchloride In water	97.2%

methanesulfonic acid (75-75-2) + 2-(6-((cyclopropylmethyl)carbamoyl)-2-(methoxycarbonyl)pyridin-3-yl)-4-methoxy-5-vinyl benzoic acid + 4-aminobenzamidine dihydrochloride (2498-50-2) → methyl 3-[2-(4-carbamimidoylphenylcarbamoyl)-5-methoxy-4-vinylphenyl]-6-(cyclopropylmethylcarbamoyl)pyridine-2-carboxylate methanesulfonate

Conditions	Yield
Stage #1: 2-(6-((cyclopropylmethyl)carbamoyl)-2-(methoxycarbonyl)pyridin-3-yl)-4-methoxy-5-vinyl benzoic acid; 4-aminobenzamidine dihydrochloride With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In isopropyl alcohol at 0 - 20℃; for 31h; Stage #2: methanesulfonic acid In methanol; isopropyl alcohol at 0 - 20℃; for 1h;	94%
Stage #1: 2-(6-((cyclopropylmethyl)carbamoyl)-2-(methoxycarbonyl)pyridin-3-yl)-4-methoxy-5-vinyl benzoic acid; 4-aminobenzamidine dihydrochloride With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In isopropyl alcohol at 20℃; for 13h; Large scale; Stage #2: methanesulfonic acid In methanol Large scale;	93%

succinic acid anhydride (108-30-5) + 4-aminobenzamidine dihydrochloride (2498-50-2) → 4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid, monohydrochloride

Conditions	Yield
With pyridine; dmap In N,N-dimethyl-formamide at 100℃; for 0.5h;	88%

N-[[2-(chloromethyl)-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridyl-β-alanine ethyl ester (1307233-94-8) + 4-aminobenzamidine dihydrochloride (2498-50-2) → 3-({2-[(4-carbamimidoylphenylamino)methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}pyridin-2-yl-amino)propionic acid ethyl ester

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate; sodium iodide In acetic acid butyl ester; water at 40℃; for 2h; Reagent/catalyst; Inert atmosphere;	88%
With tetrabutylammomium bromide; potassium carbonate; sodium iodide In acetic acid butyl ester; water at 40℃; for 2h; Reagent/catalyst; Inert atmosphere;	88%

4-aminobenzamidine dihydrochloride (2498-50-2) + benzyl chloroformate (501-53-1) → 4-[N-(benzyloxycarbonyl)-aminoiminomethyl]aniline (147291-70-1)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; dichloromethane; water	87%
With sodium hydroxide In tetrahydrofuran; water for 1h; Ambient temperature;	50%

4-aminobenzamidine dihydrochloride (2498-50-2) → p-Azidobenzamidin

Conditions	Yield
Stage #1: 4-aminobenzamidine dihydrochloride With hydrogenchloride; sodium nitrite In water at 0℃; for 1h; Inert atmosphere; Stage #2: With sodium azide In water for 1.83h; Inert atmosphere;	87%

2-phenylethynylaniline (13141-38-3) + 4-aminobenzamidine dihydrochloride (2498-50-2) → (E)-4-(3-(2-(phenylethynyl)phenyl)triaz-1-enyl)benzimidamide

Conditions	Yield
Stage #1: 4-aminobenzamidine dihydrochloride With hydrogenchloride In water at 0℃; for 0.25h; Stage #2: With sodium nitrite In water at 0℃; for 0.25h; Stage #3: 2-phenylethynylaniline Further stages;	85%

methanol (67-56-1) + [(p-methylphenyl)sulfonylmethyl]isonitrile (38622-91-2, 36635-61-7) + 4-aminobenzamidine dihydrochloride (2498-50-2) + 3-ethoxy-4-(2-dimethylaminoethoxy)benzaldehyde (86759-23-1) → (4-Carbamimidoylphenylamino)-(4-(2-dimethylaminoethoxy)-3-ethoxyphenyl)acetic acid methyl ester (883575-39-1)

Conditions	Yield
Stage #1: 4-aminobenzamidine dihydrochloride; 3-ethoxy-4-(2-dimethylaminoethoxy)benzaldehyde In methanol at 60℃; for 0.5h; Stage #2: methanol; [(p-methylphenyl)sulfonylmethyl]isonitrile; boron trifluoride diethyl etherate at 0 - 20℃; for 48h; Stage #3: With ammonia; water In methanol; ethyl acetate	83%

gloutaric dichloride (2873-74-7) + 4-aminobenzamidine dihydrochloride (2498-50-2) → N,N'-[4,4'-(amidinobisphenyl)]pentanediamide dihydrochloride

Conditions	Yield
Stage #1: 4-aminobenzamidine dihydrochloride With pyridine In N,N-dimethyl-formamide for 0.25h; Stage #2: gloutaric dichloride In N,N-dimethyl-formamide for 1.25h; Product distribution / selectivity; Heating / reflux;	80%

4-aminobenzamidine dihydrochloride (2498-50-2) + chloroformic acid ethyl ester (541-41-3) → ethyl ((4-aminophenyl)(imino)methyl)carbamate

Conditions	Yield
With sodium hydroxide In water; acetone at 0 - 10℃; for 0.333333h;	75%

2-(6-((cyclopropylmethyl)carbamoyl)-2-((2-morpholinoethoxy)carbonyl)pyridin-3-yl)-4-methoxy-5-vinylbenzoic acid + 4-aminobenzamidine dihydrochloride (2498-50-2) → 2-morpholinoethyl 3-(2-((4-carbamimidoylphenyl)carbamoyl)-5-methoxy-4-vinylphenyl)-6-((cyclopropylmethyl)carbamoyl)picolinate hydrochloride

Conditions	Yield
Stage #1: 2-(6-((cyclopropylmethyl)carbamoyl)-2-((2-morpholinoethoxy)carbonyl)pyridin-3-yl)-4-methoxy-5-vinylbenzoic acid; 4-aminobenzamidine dihydrochloride With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: With hydrogenchloride	72%

5,8-dichloro-2,3-diacyanoquinoxaline (1140899-25-7) + 4-aminobenzamidine dihydrochloride (2498-50-2) → 4-amino-6,9-dichloro-2-(4-aminophenyl)benzo[g]pteridine

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 80℃; for 12h;	71%

4-aminobenzamidine dihydrochloride (2498-50-2) + Methacryloyl chloride (920-46-7) → N-methacryloyl-4-aminobenzamidine

Conditions	Yield
With pyridine In N,N-dimethyl acetamide at 0 - 20℃; for 2h; Inert atmosphere;	71%

p-nitrophenylcarbonate hexyl ester (67036-15-1) + 4-aminobenzamidine dihydrochloride (2498-50-2) → hexyl ((4-aminophenyl)(imino)methyl)carbamate

Conditions	Yield
With sodium hydroxide In water; acetone at 20℃;	69%

4-aminobenzamidine dihydrochloride (2498-50-2) + acetic acid 4-nitro-phenoxycarbonyl-oxymethyl ester (101623-70-5) → ((((4-aminophenyl)(imino)methyl)carbamoyl)oxy)methyl acetate

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide	67%

tert-butyl 2-((4R,6S)-2,2-dimethyl-6-((((4-nitrophenoxy)carbonyl)oxy)methyl)-1,3-dioxan-4-yl)acetate + 4-aminobenzamidine dihydrochloride (2498-50-2) → tert-butyl 2-((4R,6S)-6-(((((4-aminophenyl)(imino)methyl)carbamoyl)oxy)methyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate

Conditions	Yield
With sodium hydroxide In water; acetone at 20℃;	66%

4-aminobenzamidine dihydrochloride (2498-50-2) + 2-(2H-benzotriazol-2-yl)-3-dimethylamino-N,N-dimethyl-prop-2-eniminiumtetrafluoroborate → 4-(5-Benzotriazol-2-yl-pyrimidin-2-yl)-phenylamine

Conditions	Yield
With pyridine for 2h; Heating;	65%

2-(6-((cyclopropylmethyl)carbamoyl)-2-(methoxycarbonyl)pyridin-3-yl)-4-methoxy-5-vinyl benzoic acid + 4-aminobenzamidine dihydrochloride (2498-50-2) → methyl-3-(2-(4-carbamimidoylphenylcarbamoyl)-5-methoxy-4-vinylphenyl)-6-(cyclopropylmethylcarbamoyl)-2-picolinate

Conditions	Yield
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃;	65%

2-(6-((cyclopropylmethyl)carbamoyl)-2-(methoxycarbonyl)pyridin-3-yl)-4-methoxy-5-vinyl benzoic acid + 4-aminobenzamidine dihydrochloride (2498-50-2) → methyl 3-(2-((4-carbamimidoylphenyl)carbamoyl)-5-methoxy-4-vinylphenyl)-6-((cyclopropylmethyl)-carbamoyl)picolinate hydrochloride

Conditions	Yield
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;	65%
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at -1.1 - 0.3℃; for 22h;

2-(6-((cyclopropylmethyl)carbamoyl)-2-((2-methyl-1-(pivaloyloxy)propoxy)carbonyl)pyridin-3-yl)-4-methoxy-5-vinylbenzoic acid + 4-aminobenzamidine dihydrochloride (2498-50-2) → 2-methyl-1-(pivaloyloxy)propyl 3-(2-((4-carbamimidoylphenyl)carbamoyl)-5-methoxy-4-vinylphenyl)-6-((cyclopropylmethyl)carbamoyl)picolinate hydrochloride

Conditions	Yield
Stage #1: 2-(6-((cyclopropylmethyl)carbamoyl)-2-((2-methyl-1-(pivaloyloxy)propoxy)carbonyl)pyridin-3-yl)-4-methoxy-5-vinylbenzoic acid; 4-aminobenzamidine dihydrochloride With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: With hydrogenchloride	65%

tert-butyl 3-(((4-nitrophenoxy)carbonyl)oxy)propanoate + 4-aminobenzamidine dihydrochloride (2498-50-2) → tert-butyl 3-((((4-aminophenyl)(imino)methyl)carbamoyl)oxy)propanoate

Conditions	Yield
With sodium hydroxide In water; acetone at 20℃;	61%

4-aminobenzamidine dihydrochloride (2498-50-2) + acryloyl chloride (814-68-6) → (4-acrylamidophenyl)(amino)methaniminium chloride

Conditions	Yield
With sodium acetate In water at 5℃; for 1h;	60%
With sodium acetate In water at 5℃; for 1h;	52%
With sodium acetate In water at 5℃;

4,6-dichloro-5-nitropyrimidine (4316-93-2) + 4-aminobenzamidine dihydrochloride (2498-50-2) → C18H17N9O2*2ClH

Conditions	Yield
With triethylamine In ethanol at 50℃; for 3h;	60%

3-methoxy-4-(phenylmethoxy)benzaldehyde (2426-87-1) + 4-aminobenzamidine dihydrochloride (2498-50-2) + phosphorous acid trimethyl ester (121-45-9) → [(4-benzyloxy-3-methoxyphenyl)(4-carbamimidoylphenylamino)methyl]phosphonic acid dimethyl ester hydrochloride

Conditions	Yield
Stage #1: 3-methoxy-4-(phenylmethoxy)benzaldehyde; 4-aminobenzamidine dihydrochloride; phosphorous acid trimethyl ester With acetic acid at 20℃; for 48h; Stage #2: With hydrogenchloride In water at 4℃;	58%

3-((4-fluorophenyl)ethynyl)aniline + 4-aminobenzamidine dihydrochloride (2498-50-2) → (E)-4-(3-(3-((4-fluorophenyl)ethynyl)phenyl)triaz-1-enyl)benzimidamide

Conditions	Yield
Stage #1: 4-aminobenzamidine dihydrochloride With hydrogenchloride In water at 0℃; for 0.25h; Stage #2: With sodium nitrite In water at 0℃; for 0.25h; Stage #3: 3-((4-fluorophenyl)ethynyl)aniline Further stages;	58%

p-benzyloxybenzaldehyde (4397-53-9) + 4-aminobenzamidine dihydrochloride (2498-50-2) → 4-(4-benzyloxybenzylamino)benzimidamide

Conditions	Yield
Stage #1: p-benzyloxybenzaldehyde; 4-aminobenzamidine dihydrochloride With acetic acid; N-ethyl-N,N-diisopropylamine In ethanol at 20℃; Stage #2: With sodium cyanoborohydride In ethanol at 20℃;	57%

di-tert-butyl dicarbonate (24424-99-5) + 4-aminobenzamidine dihydrochloride (2498-50-2) → tert-butyl [(4-aminophenyl)(imino)methyl]carbamate (147291-56-3)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran for 5h;	56%
Stage #1: 4-aminobenzamidine dihydrochloride With sodium hydroxide In tetrahydrofuran; water at 0 - 10℃; for 0.5h; Inert atmosphere; Stage #2: di-tert-butyl dicarbonate In tetrahydrofuran; water at 0 - 10℃; for 3h; Inert atmosphere;	56.3 g

Upstream product

• 619-72-7 4-nitrobenzonitrile 
• 52708-02-8 4-nitrobenzimidic acid methyl ester 
• 25412-75-3 4-nitrobenzamidine 
• 35704-19-9 N-(4-cyanophenyl)acetamide 
• 873-74-5 4-Aminobenzonitrile 
• 15723-90-7 4-nitrobenzamidine hydrochloride 

Downstream Products

• 133118-43-1 2-<2-(4-aminophenyl)-4-imidazolyl>ethanamine 
• 153982-08-2 4-<<4-(aminoiminomethyl)phenyl>amino>-4-oxobutanoic acid 
• 147291-56-3 tert-butyl [(4-aminophenyl)(imino)methyl]carbamate 
• 125772-46-5 4-aminobenzamidinium formate 
• 125772-53-4 4-aminobenzamidinium acetate 
• 125772-67-0 4-aminobenzamidinium pyruvate 
• 406203-78-9 N-(4-carbamimidoyl-phenyl)-2-phenyl-malonamic acid benzyl ester 
• 149193-63-5 4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxo-buten-(E)-oic acid 
• 60218-18-0 2-(4-aminophenyl)-4-hydroxy-5-pyrimidine carboxylic acid 
• 1013333-13-5 C₂HF₃O₂*C₁₅H₁₇N₃O₇ 
• 1214258-85-1 6-(4-aminophenyl)-4-thioxo-3,4-dihydro-1,3,5-triazin-2(1H)-one 
• 1032471-04-7 N,N'-bis[4-(aminoiminomethyl)phenyl]pentane-1,5-dicarboxamide 

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