524-36-7

Basic information

• Product Name: Pyridoxamine dihydrochloride
• Synonyms: 2-methyl-3-hydroxy-4-aminomethyl-5-hydroxymethylpyridenedihydrochloride;4-(aminomethyl)-5-hydroxy-6-methyl-3-pyridinemethanodihydrochloride;4-(AMINOMETHYL)-5-HYDROXY-6-METHYL-3-PYRIDENEMETHANOL DIHYDROCHLORIDE;4-AMINOMETHYL-5-HYDROXY-6-METHYL-3-PYRIDINEMETHANOL DIHYDROCHLORIDE;PYRIDOXAMINE;PYRIDOXAMINE DIHYDROCHLORIDE;Pyridoxamine DiHCl;4-(Aminomethyl)-5-Hydroxy-6-Methyl-3-Pyridenemetha
• CAS NO: 524-36-7
• Molecular Formula: C₈H₁₄N₂O₂*2Cl
• Molecular Weight: 241.11
• EINECS: 208-357-6
• Product Categories: Aromatics Compounds;Pyridinium Compounds;Vitamins and derivatives;Aromatics;Bases & Related Reagents;Nucleotides;Isolabel
• Mol File: 524-36-7.mol

Chemical Properties

• Melting Point: 224-226 °C (dec.)(lit.)
• Boiling Point: 460.1 °C at 760 mmHg
• Flash Point: 232.1 °C
• Appearance: White to off-white to pale brown/Powder or Solid
• Density: 1.4025 (rough estimate)
• Vapor Pressure: 2.92E-09mmHg at 25°C
• Refractive Index: 1.6100 (estimate)
• Storage Temp.: −20°C
• Solubility: DMSO (Slightly), Methanol (Slightly), Water (Slightly)
• PKA: pKa 3.31(H2O t = 25 I = 0.1)(Approximate)
• Water Solubility: Soluble in DMSO, water, or methanol /n
• Merck: 7980
• BRN: 3632748
• CAS DataBase Reference: Pyridoxamine dihydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Pyridoxamine dihydrochloride(524-36-7)
• EPA Substance Registry System: Pyridoxamine dihydrochloride(524-36-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 2
• RTECS: UV1230000
• HazardClass: IRRITANT
• Hazardous Substances Data: 524-36-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Applications:
Pyridoxamine dihydrochloride is used as a therapeutic agent for the treatment of diabetic nephropathy. It blocks pathogenic oxidative pathways in the progression of the disease and has been shown to slow down the progression of diabetic kidney disease (DKD) in patients with relatively preserved kidney function (i.e., baseline SCr 1.3 to 1.9 mg/dL).
Used in Organic Synthesis:
Pyridoxamine dihydrochloride (CAS# 524-36-7) is a compound that is useful in organic synthesis, contributing to the development of various chemical compounds and products.
Used in Mammalian Cell Culture:
Pyridoxamine dihydrochloride is used as an alternative to pyridoxine or pyridoxal in mammalian cell culture. Vitamin B6 is a required component of cell culture media, and historically, media have been supplemented with the aldehyde form, pyridoxal. However, pyridoxal is unstable in liquid media, making pyridoxamine a preferred supplement when cells can utilize either pyridoxine and/or pyridoxamine. A number of classical media are now offered with a choice between pyridoxal and pyridoxine as the vitamin B6 source.
Chemical Properties:
Pyridoxamine dihydrochloride is a white crystalline powder that can be obtained by combining pyridoxamine with two molar equivalents of hydrochloric acid.

Preparation

The invention relates to a preparation method of pyridoxamine dihydrochloride, belonging to the technical field of the preparation of water soluble vitamins. The preparation method comprises the following steps: preparing pyridoxal oxime: taking pyridoxine hydrochloride as initial raw material and water as a reaction medium, adding activated manganese dioxide and concentrated sulfuric acid to generate pyridoxal by the reaction, and then reacting with anhydrous sodium acetate and hydroxylamine hydrochloride to obtain pyridoxal oxime; preparing pyridoxamine dihydrochloride: firstly enabling pyridoxal oxime to react with acetic acid and zinc to obtain acetic acid solution containing pyridoxamine, then decompressing the solution and reclaiming the acetic acid to obtain slurry concentrate, decompressing and reclaiming the acetic acid again to obtain pyridoxamine water solution, regulating the pH value to be alkaline so as to separate pyridoxamine out, adding water and hydrochloric acid after vacuum filteration, decoloring and filtering to obtain filtrate, decompressing and concentrating the filtrate until white solids are separated out, adding solvent and stirring, and finally crystallizing at the lower temperature, filtering and drying to obtain the pyridoxamine dihydrochloride. The invention has the advantages that the prepared pyridoxamine dihydrochloride has high total mol yield and purity, and the preparation method is reduced.https://patents.google.com/patent/CN101628892A/en

Purification Methods

The amine salt is crystallised from hot MeOH. The free base crystallises from EtOH with m 193-193.5o [Harris et al. J Biol Chem 154 315 1944, J Am Chem Soc 66 2088 1944]. [Beilstein 22 IV 6064, 22/12 V 324.]

InChI:InChI=1/C8H12N2O2.2ClH/c1-5-8(12)7(2-9)6(4-11)3-10-5;;/h3,11-12H,2,4,9H2,1H3;2*1H

Synthetic route

2-Methyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine oxime (20905-66-2) → pyridoxamine dihydrochloride (524-36-7)

Conditions	Yield
With hydrogenchloride; hydrogen; palladium on activated charcoal In methanol for 0.916667h;	95.2%

N-acetylpyridoxamine hydrochloride → pyridoxamine dihydrochloride (524-36-7)

Conditions	Yield
With hydrogenchloride In methanol at 39 - 48℃; for 10 - 16h; Heating / reflux; Industry scale;	91%

2-methyl-3-hydroxy-4-cyano-5-acetyloxymethyl-pyridine (408335-89-7) → pyridoxamine dihydrochloride (524-36-7)

Conditions	Yield
With hydrogenchloride; hydrogen; 5%-palladium/activated carbon In methanol; water at 20℃; under 760.051 Torr;	83%
With hydrogenchloride; 5%-palladium/activated carbon; hydrogen In methanol; water at 20℃;	83%
With hydrogenchloride; 5%-palladium/activated carbon; hydrogen In methanol; water at 20℃; under 760.051 Torr;	83%

pyridoxal hydrochloride (58-56-0) → pyridoxamine dihydrochloride (524-36-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) MnO2, 0.3 M H2SO4, 2.) NH2OH*HCl / 1.) 5 h, 2.) 70 deg C, 10 min 2: 95.2 percent / HCl, H2 / 5percent Pd/C / methanol / 0.92 h View Scheme

C20H18N2O6 (863030-57-3) → pyridoxamine dihydrochloride (524-36-7)

Conditions	Yield
Stage #1: C20H18N2O6 With propylamine In tetrahydrofuran at 50 - 70℃; for 18 - 20h; Gabriel Synthesis; Stage #2: With hydrogenchloride In methanol; isopropyl alcohol at 45 - 65℃; for 5 - 8h;

di-tert-butyl dicarbonate (24424-99-5) + pyridoxamine dihydrochloride (524-36-7) → Carbonic acid 4-(tert-butoxycarbonylamino-methyl)-5-hydroxymethyl-2-methyl-pyridin-3-yl ester tert-butyl ester (176754-73-7)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane at 0 - 25℃; for 12h; pH 9.5;	100%

pyridoxamine dihydrochloride (524-36-7) → pyridoxamine (85-87-0)

Conditions	Yield
With sodium hydroxide In water pH=9;	100%
With sodium hydrogencarbonate In water	87%

di-tert-butyl dicarbonate (24424-99-5) + pyridoxamine dihydrochloride (524-36-7) → (3-hydroxy-5-hydroxymethyl-2-methylpyridin-4-yl)methylcarbamic acid tert-butyl ester (210034-86-9)

Conditions	Yield
With triethylamine In methanol; dichloromethane at 20℃; for 2h;	95%

pyridoxamine dihydrochloride (524-36-7) + salicylaldehyde (90-02-8) → 4-(((2-hydroxybenzylidene)amino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol

Conditions	Yield
Stage #1: pyridoxamine dihydrochloride With potassium hydroxide In methanol for 0.5h; pH=Ca. 9; Stage #2: salicylaldehyde In methanol; chloroform at 50℃; for 3h;	91%

pyridoxamine dihydrochloride (524-36-7) → 2-methyl-3-hydroxy-4-(aminomethyl)-5-(bromomethyl)pyridine dihydrobromide (1198-25-0)

Conditions	Yield
With hydrogen bromide for 0.75h; Heating;	87%
With hydrogen bromide for 2h; Heating;	81%
With hydrogen bromide
With hydrogen bromide

pyridoxamine dihydrochloride (524-36-7) + pyridoxal hydrochloride (65-22-5) → Schiff base pyridoxal-pyridoxamine (122908-64-9)

Conditions	Yield
With potassium hydroxide for 0.5h; Ambient temperature;	80%

2-hydroxy-5-methylbenzaldehyde (613-84-3) + pyridoxamine dihydrochloride (524-36-7) + di(n-butyl)tin oxide (818-08-6) → 13,13-di-n-butyl-4-hydroxymethyl-1,9-dimethyl-5H-benzo[i]pyrido[4,3-d]-12,14,6,2-dioxazaestanocine

Conditions	Yield
With potassium hydroxide In methanol; toluene for 8h; Reflux;	78.6%

pyridoxamine dihydrochloride (524-36-7) + di(n-butyl)tin oxide (818-08-6) + salicylaldehyde (90-02-8) → 13,13-di-n-butyl-4-hydroxymethyl-1-methyl-5H-benzo[i]pyrido[4,3-d]-12,14,6,2-dioxazaestanocine

Conditions	Yield
With potassium hydroxide In methanol; toluene for 8h; Reflux;	67.2%

2-oxoheptadecanoic acid (73506-86-2) + pyridoxamine dihydrochloride (524-36-7) → N-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methyl)palmitamide

Conditions	Yield
With tert.-butylhydroperoxide In methanol; water at 20℃; for 12h; Sealed tube; Darkness; chemoselective reaction;	67%

pyridoxamine dihydrochloride (524-36-7) + di(n-butyl)tin oxide (818-08-6) + 5-chlorosalicyclaldehyde (635-93-8) → 13,13-di-n-butyl-9-chloro-4-hydroxymethyl-1-methyl-5H-benzo[i]pyrido[4,3-d]-12,14,6,2-dioxazaestanocine

Conditions	Yield
With potassium hydroxide In methanol; toluene for 8h; Reflux;	65.3%

pyridoxamine dihydrochloride (524-36-7) + di(n-butyl)tin oxide (818-08-6) + 5-Nitrosalicylaldehyde (97-51-8) → 13,13-di-n-butyl-4-hydroxymethyl-1-methyl-9-nitro-5H-benzo[i]pyrido[4,3-d]-12,14,6,2-dioxazaestanocine

Conditions	Yield
With potassium hydroxide In methanol; toluene for 8h; Reflux;	65.3%

pyridoxamine dihydrochloride (524-36-7) + di(n-butyl)tin oxide (818-08-6) + 5-bromosalicyclaldehyde (1761-61-1) → 13,13-di-n-butyl-9-bromo-4-hydroxymethyl-1-methyl-5H-benzo[i]pyrido[4,3-d]-12,14,6,2-dioxazaestanocine

Conditions	Yield
With potassium hydroxide In methanol; toluene for 8h; Reflux;	61.5%

2-hydroxy-5-methoxybenzaldehyde (672-13-9) + pyridoxamine dihydrochloride (524-36-7) + di(n-butyl)tin oxide (818-08-6) → 13,13-di-n-butyl-4-hydroxymethyl-9-methoxy-1-methyl-5H-benzo[i]pyrido[4,3-d]-12,14,6,2-dioxazaestanocine

Conditions	Yield
With potassium hydroxide In methanol; toluene for 8h; Reflux;	60.5%

4-chloro-1-[2-chloro-2-(4-fluorophenyl)ethyl]-1H-pyrazolo[3,4-d]-pyrimidine (1013930-73-8) + pyridoxamine dihydrochloride (524-36-7) → (Z)-4-((1-(4-fluorostyryl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (1451010-34-6)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 150℃; for 0.166667h; Microwave irradiation; Inert atmosphere;	58%

5-iodosalicyclaldehyde (1761-62-2) + pyridoxamine dihydrochloride (524-36-7) + di(n-butyl)tin oxide (818-08-6) → 13,13-di-n-butyl-4-hydroxymethyl-9-iodo-1-methyl-5H-benzo[i]pyrido[4,3-d]-12,14,6,2-dioxazaestanocine

Conditions	Yield
With potassium hydroxide In methanol; toluene for 8h; Reflux;	56.7%

all-trans-retinoic-acid (302-79-4) + pyridoxamine dihydrochloride (524-36-7) → 3,7-dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid (3-hydroxy-5-hydroxymethyl-2-methyl-pyridin-4-ylmethyl)-amide

Conditions	Yield
Stage #1: all-trans-retinoic-acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.166667h; Stage #2: pyridoxamine dihydrochloride With triethylamine In dichloromethane at 20℃;	45%

2-hydroxy-5-t-butylbenzaldehyde (2725-53-3) + pyridoxamine dihydrochloride (524-36-7) + di(n-butyl)tin oxide (818-08-6) → 13,13-di-n-butyl-9-t-butyl-4-hydroxymethyl-1-methyl-5H-benzo[i]pyrido[4,3-d]-12,14,6,2-dioxazaestanocine

Conditions	Yield
With potassium hydroxide In methanol; toluene for 8h; Reflux;	40.3%

2-(3,4-dihydroxyphenyl)-2-hydroxyacetaldehyde (13023-73-9) + pyridoxamine dihydrochloride (524-36-7) → C16H18N2O5*ClH

Conditions	Yield
With sodium hydrogencarbonate In water at 20℃; for 18h;	27%

pyridoxamine dihydrochloride (524-36-7) → pyridoxal hydrochloride (58-56-0)

Conditions	Yield
With sulfuric acid; water; sodium nitrite at 20 - 90℃; for 2h;	25%

pyridoxamine dihydrochloride (524-36-7) + cytosine arabinoside-5'-monophosphate (7075-11-8) → C17H24N5O9P (1421929-65-8)

Conditions	Yield
Stage #1: pyridoxamine dihydrochloride With sodium hydrogencarbonate In water Stage #2: cytosine arabinoside-5'-monophosphate With dicyclohexyl-carbodiimide In water; tert-butyl alcohol Reflux;	25%

pyridine (110-86-1) + pyridoxamine dihydrochloride (524-36-7) + n-decanoyl chloride (112-13-0) → 4-(decanoylamino-methyl)-3-decanoyloxy-5-decanoyloximethyl-2-methyl-pyridine (104622-70-0)

Conditions	Yield
With chloroform

2-furancarbonyl chloride (527-69-5) + pyridoxamine dihydrochloride (524-36-7) → 4-[(furan-2-carbonylamino)-methyl]-3-(furan-2-carbonyloxy)-5-(furan-2-carbonyloximethyl)-2-methyl-pyridine (114493-09-3)

Conditions	Yield
With pyridine

pyridoxamine dihydrochloride (524-36-7) → pyridoxamine-5'-phosphate (529-96-4)

Conditions	Yield
With phosphoric acid; phosphorus pentoxide at 60℃;
With trichlorophosphate
With phosphoric acid; phosphorus pentoxide room temp., 1 h; 65 deg C, 2.5 h; Yield given;

pyridoxamine dihydrochloride (524-36-7) + acetic anhydride (108-24-7) → 3-acetoxy-5-acetoxymethyl-4-(acetylamino-methyl)-2-methyl-pyridine; hydrochloride

Conditions	Yield
With acetic acid

pyridoxamine dihydrochloride (524-36-7) + benzaldehyde (100-52-7) → [4-(benzylidenamino-methyl)-5-hydroxy-6-methyl-[3]pyridyl]-methanol

Conditions	Yield
With potassium hydroxide

pyridoxamine dihydrochloride (524-36-7) + benzoyl chloride (98-88-4) → 4-(benzoylamino-methyl)-3-benzoyloxy-5-benzoyloxymethyl-2-methyl-pyridine (21901-57-5)

Conditions	Yield
With pyridine; chloroform

pyridoxamine dihydrochloride (524-36-7) + 4-nitro-benzoyl chloride (122-04-3) → 2-methyl-4-[(4-nitro-benzoylamino)-methyl]-3-(4-nitro-benzoyloxy)-5-(4-nitro-benzoyloximethyl)-pyridine (104176-11-6)

Conditions	Yield
With pyridine; chloroform

Upstream product

• 66-72-8 pyridoxal 
• 863030-57-3 C₂₀H₁₈N₂O₆ 
• 20905-66-2 2-Methyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine oxime 
• 58-56-0 pyridoxal hydrochloride 
• 408335-89-7 2-methyl-3-hydroxy-4-cyano-5-acetyloxymethyl-pyridine 

Downstream Products

• 529-96-4 pyridoxamine-5'-phosphate 
• 21901-57-5 4-(benzoylamino-methyl)-3-benzoyloxy-5-benzoyloxymethyl-2-methyl-pyridine 
• 85-87-0 pyridoxamine 
• 58-56-0 pyridoxal hydrochloride 
• 1451010-34-6 (Z)-4-((1-(4-fluorostyryl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol 
• 54-47-7 pyridoxal 5'-phosphate 
• 88328-23-8 2,4-bis(3'-hydroxy-5'-hydroxymethyl-2'-methyl-4'-pyridyl)-7-phenyl-6,8-dioxo-3,7-diazabicyclo<3.3.0>octane 
• 176754-77-1 Carbonic acid 5-{(S)-2-amino-2-[((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-carbamoyl]-ethyl}-4-(tert-butoxycarbonylamino-methyl)-2-methyl-pyridin-3-yl ester tert-butyl ester 
• 176754-78-2 Carbonic acid 4-(tert-butoxycarbonylamino-methyl)-5-{(S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-2-[((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-carbamoyl]-ethyl}-2-methyl-pyridin-3-yl ester tert-butyl ester 
• 122908-64-9 Schiff base pyridoxal-pyridoxamine 
• 104176-11-6 2-methyl-4-[(4-nitro-benzoylamino)-methyl]-3-(4-nitro-benzoyloxy)-5-(4-nitro-benzoyloximethyl)-pyridine 

Relevant articles and documents

Fabrication of ω-Transaminase@Metal-Organic Framework Biocomposites for Efficiently Synthesizing Benzylamines and Pyridylmethylamines

In this study, ten ω-transaminases (ω-TAs) have been investigated to efficiently catalyze the synthesis of twenty-four functionalized benzylamines and pyridylmethylamines. We optimized the reactions, screened suitable amino donors and compared ω-transaminases activities for all aromatic aldehyde substrates. Under the optimized conditions, eighteen aromatic amines have been obtained with 60.4%–96.6% conversions and isolated only via simple extraction and recrystallization with 18.5%–81% yields on a preparative scale. Furthermore, we first immobilized the Bm-STA onto the MOFs via the physical adsorption to overcome the limitation of free enzyme and improve their industrial applications. The obtained Bm-STA/UiO-66-NH2 composites exhibited not only high enzymes loading (80.4 mg g?1) and enzyme activity recovery (95.8%), but also the better reusability, storage stability, pH stability and the tolerance to acetone and DMF.

COMPOSITIONS AND METHODS FOR THE TREATMENT OF METABOLIC DISORDERS

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for treating or preventing metabolic disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be also used to the treatment of diabetes, lipid peroxidation, hypertriglyceridemia, metabolic disorders, free radical generated due to reactive oxygen and carbonyl groups, ionizing radiation, advanced glycation end products, kidney disease, renal complications and kidney stone disease.

COMPOSITIONS AND METHODS FOR THE TREATMENT OF METABOLIC DISORDERS

The invention relates to the compounds of formula (I) or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula (I), and methods for treating or preventing metabolic disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be also used to the treatment of diabetes, lipid peroxidation, hypertriglyceridemia, metabolic disorders, free radical generated due to reactive oxygen and carhonyl groups, ionizing radiation, advanced glycation end products, kidney disease, renal complications and kidney stone disease.

MANUFACTURE OF VITAMIN B6

The present invention relates to a process for the manufacture of pyridoxamine, pyridoxine and further clodely related 3-hydroxy-pyridine derivatives and of acid salts thereof. Pyridoxamine and pyridoxine belong to the vitamin B6 group. This new multistep process is represented schematically in the following Reaction Scheme (formula (I)).

METHODS FOR THE SYNTHESIS OF PYRIDOXAMINE

The invention provides non-oxidative methods for the large scale manufacture of pyridoxamine (I) (4-aminomethyl-3-hydroxy-5-hydroxymethyl-2-methylpyridine): Formula (I), and salts thereof. The invention also provides intermediate compounds for the synthesis of pyridoxamine, as well as compositions and methods for the treatment and/or prevention of conditions associated with the formation of post-Amadori advanced glycation end-products.