332-80-9

Basic information

• Product Name: 1-Methyl-L-histidine
• Synonyms: METHYLHISTIDINE, L-1-;METHYLHISTIDINE, L-3-;1-METHYL-L-HISTIDINE;1-METHYLHISTIDINE;3-(1-METHYLIMIDAZOL-4-YL)-L-ALANINE;3-(1-METHYLIMIDAZOL-5-YL)-L-ALANINE;3-METHYL-L-HISTIDINE;P-METHYL-L-HISTIDINE
• CAS NO: 332-80-9
• Molecular Formula: C₇H₁₁N₃O₂
• Molecular Weight: 169.18
• EINECS: 206-368-0
• Product Categories: Pharmaceutical Raw Materials;Histidine [His, H];Amino Acids and Derivatives;Amino acids methyl、ethyl、t-butyl series;Amino Acids & Derivatives;Heterocycles;Inhibitors
• Mol File: 332-80-9.mol
• Article Data: 7

Chemical Properties

• Melting Point: ~240 °C (dec.)(lit.)
• Boiling Point: 298.47°C (rough estimate)
• Flash Point: 204.8 °C
• Appearance: /
• Density: 1.2509 (rough estimate)
• Vapor Pressure: 1.25E-07mmHg at 25°C
• Refractive Index: 1.5950 (estimate)
• Storage Temp.: 2-8°C(protect from light)
• Solubility: Methanol (Slightly), Water (Slightly, Sonicated)
• PKA: 1.69(at 25℃)
• Stability: Hygroscopic
• BRN: 9727
• CAS DataBase Reference: 1-Methyl-L-histidine(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Methyl-L-histidine(332-80-9)
• EPA Substance Registry System: 1-Methyl-L-histidine(332-80-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-24/25-22
• WGK Germany: 3
• Hazardous Substances Data: 332-80-9(Hazardous Substances Data)

Usage

Description

1-Methyl-L-histidine is a natural, non-proteinogenic amino acid that is found as a component of certain proteins, particularly in muscle tissues. It is characterized by its beige powder form and is known for its role in muscle protein breakdown, making it a significant compound in the study of muscle metabolism and related conditions.

Uses

Used in Medical Research:
1-Methyl-L-histidine is used as a biomarker for skeletal muscle toxicity. Its presence in urine, particularly as a metabolite, is highly correlated with the sex-, dose-, and time-dependent development of myotoxicity, which is muscle toxicity often associated with the use of certain medications like cerivastatin.
Used in Muscle Metabolism Studies:
As an index of muscle protein breakdown, 1-Methyl-L-histidine is employed in the study of muscle metabolism. Understanding its role in this process can help researchers and medical professionals develop better strategies for managing muscle wasting conditions and muscle-related diseases.
Used in Pharmaceutical Development:
Given its correlation with muscle toxicity and its role in protein breakdown, 1-Methyl-L-histidine may also be used in the development of pharmaceuticals aimed at treating or preventing muscle-related disorders, particularly those that involve muscle wasting or myotoxicity.

InChI:InChI=1/C7H11N3O2/c1-10-3-5(9-4-10)2-6(8)7(11)12/h3-4,6H,2,8H2,1H3,(H,11,12)

Synthetic route

(S)-7-(methoxycarbonyl)-2-methyl-5-oxo-5,6,7,8-tetrahydroimidazo[1,5-c] pyrimidin-2-ium iodide (69618-95-7) → His(1-CH3) (332-80-9)

Conditions	Yield
With hydrogenchloride Heating;	99%

Nα-Trityl-Nτ-methyl-L-histidin (118891-68-2) → His(1-CH3) (332-80-9)

Conditions	Yield
With acetic acid In water; ethyl acetate for 1h; Heating;	71%

L-histidine (71-00-1) + methyl iodide (74-88-4) → 3-methyl-L-histidine (368-16-1) + His(1-CH3) (332-80-9)

Conditions	Yield
With ammonia; sodium

(S)-2-Amino-3-{5-[5-((S)-2-amino-2-carboxy-ethyl)-3-methyl-3H-imidazol-4-yldisulfanyl]-1-methyl-1H-imidazol-4-yl}-propionic acid (83471-81-2) → His(1-CH3) (332-80-9)

Conditions	Yield
With nickel In ethanol for 0.5h; Heating;

1-methyl<2-(3)H>-L-histidine (124017-72-7) → His(1-CH3) (332-80-9)

Conditions	Yield
With methylmercuric nitrate In water at 85℃; Rate constant; Mechanism; effect of pH; variation of concentration of MeHgNO3;

N-[(1,1-dimethylethoxy)carbonyl]-3-[(phenylmethoxy)methyl]-L-histidine (79950-65-5) + methyl iodide (74-88-4) → His(1-CH3) (332-80-9)

Conditions	Yield
With hydrogenchloride 1.) (DMF), 24 h, room temp., 2.) reflux, 24 h; Multistep reaction;

N(α)-benzyloxycarbonyl-N(ϖ)-t-butoxymethyl-L-histidine methyl ester (90653-43-3) + methyl iodide (74-88-4) → 3-methyl-L-histidine (368-16-1) + His(1-CH3) (332-80-9)

Conditions	Yield
With hydrogenchloride 1.) (DMF), 24 h, room temp., 2.) reflux, 24 h; Multistep reaction;

N(α)-benzyloxycarbonyl-N(ϖ)-(2-methoxyethoxy)methyl-L-histidine methyl ester (99523-88-3) + methyl iodide (74-88-4) → His(1-CH3) (332-80-9)

Conditions	Yield
Multistep reaction;

N(α)-benzyloxycarbonyl-N(ϖ)-(2-trimethylsilylethoxy)methyl-L-histidine methyl ester (99523-90-7) + methyl iodide (74-88-4) → 3-methyl-L-histidine (368-16-1) + His(1-CH3) (332-80-9)

Conditions	Yield
With hydrogenchloride 1.) (DMF), 24 h, room temp., 2.) reflux, 24 h; Multistep reaction;

N(α)-benzyloxycarbonyl-N(τ)-(2-trimethylsilylethoxy)methyl-L-histidine methyl ester (99523-91-8) + methyl iodide (74-88-4) → 3-methyl-L-histidine (368-16-1) + His(1-CH3) (332-80-9)

Conditions	Yield
With hydrogenchloride 1.) (DMF), 24 h, room temp., 2.) reflux, 24 h; Multistep reaction;

N(α)-benzyloxycarbonyl-N(ϖ)-(2,4,6-trimethylbenzyloxy)methyl-L-histidine methyl ester + methyl iodide (74-88-4) → His(1-CH3) (332-80-9)

Conditions	Yield
With hydrogenchloride 1.) (DMF), 24 h, room temp., 2.) reflux, 24 h; Multistep reaction;

1-Me-AcHis → His(1-CH3) (332-80-9)

Conditions	Yield
With (2)H8O4Pd(2+); deuteroperchloric acid In water-d2 at 40℃; Rate constant;

N(α)-benzyloxycarbonyl-N(τ)-tert-butyloxycarbonyl-L-histidine methyl ester (90653-42-2) → His(1-CH3) (332-80-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / CH2Cl2 / 1.) 0 deg C, 1 h, 2.) room temp., 3 h View Scheme

Z-His-OMe (15545-10-5) → His(1-CH3) (332-80-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 27 percent / triethylamine / ethyl acetate / 1.) 0 deg C, 1 h, 2.) room temp., 6 h. 2: 2.) 'constant boiling' hydrochloric acid / 1.) (DMF), 24 h, room temp., 2.) reflux, 24 h View Scheme

L-5-sulfanyl-1-methylhistidine (62982-24-5) → His(1-CH3) (332-80-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: air, iodide / H2O / 24 h 2: Raney Nickel / aq. ethanol / 0.5 h / Heating View Scheme

n-butyllithium (109-72-8, 29786-93-4) + His(1-CH3) (332-80-9) → (S)-methyl 2-amino-3-(1-methyl-1H-imidazol-4-yl)propanoate (57519-09-2)

Conditions	Yield
With hydrogenchloride at 20℃;	95%

formaldehyd (50-00-0) + His(1-CH3) (332-80-9) → (S)-3-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid

Conditions	Yield
With hydrogenchloride In water at 0℃; Reflux;	80%

His(1-CH3) (332-80-9) → (S)-2-Amino-3-{5-[5-((S)-2-amino-2-carboxy-ethyl)-3-methyl-3H-imidazol-4-yldisulfanyl]-1-methyl-1H-imidazol-4-yl}-propionic acid (83471-81-2)

Conditions	Yield
Stage #1: His(1-CH3) With hydrogenchloride; N-Bromosuccinimide In water at 1℃; for 0.05h; Stage #2: With tiolacetic acid In water at 0℃; for 0.5h; Stage #3: With 3-mercaptopropionic acid In water at 100℃; for 20h;	65%

His(1-CH3) (332-80-9) → [αR-2H]-Nτ-methylhistamine (1205535-89-2)

Conditions	Yield
With histidine decarboxylase; pyridoxal 5'-phosphate; water-d2 at 37℃; for 192h; pH=4.7; aq. phosphate buffer; Enzymatic reaction;	58%

Dimethoxymethane (109-87-5) + His(1-CH3) (332-80-9) → 3-methylspinacine dihydrochloride (114787-98-3)

Conditions	Yield
With hydrogenchloride 1) RT, overnight, 2) 3h, steam-bath;	45%

His(1-CH3) (332-80-9) → [αR-3H]-Nτ-methylhistamine (1205535-90-5)

Conditions	Yield
With (1)H,(3)H-water; histidine decarboxylase; pyridoxal 5'-phosphate at 37℃; for 192h; pH=4.7; aq. phosphate buffer; Enzymatic reaction;	35%

chloro-trimethyl-silane (75-77-4) + His(1-CH3) (332-80-9) → C10H19N3O2Si*ClH (118891-70-6)

Conditions	Yield
In chloroform for 1h; Heating;

peridoxal (19804-21-8) + His(1-CH3) (332-80-9) → N-pyridoxylidene-L-Nτmethylhistidine (83984-06-9)

Conditions	Yield
In methanol

bufotalin 3-hemisuberate p-nitrophenyl ester (61507-75-3) + His(1-CH3) (332-80-9) → bufotalin 3-suberoyl-L-3-methylhistidine ester (90038-13-4)

Conditions	Yield
In pyridine; water for 12h; Ambient temperature;	11 mg

His(1-CH3) (332-80-9) → 1-methyl<2-(3)H>-L-histidine (124017-72-7)

Conditions	Yield
With tritium oxide at 85℃; for 408h;

methanol (67-56-1) + His(1-CH3) (332-80-9) → L-Nτ-methylhistidine methyl ester dihydrochloride

Conditions	Yield
With thionyl chloride at 0℃; for 3h; Heating / reflux;

His(1-CH3) (332-80-9) → (S)-3-(1-Methyl-1H-imidazol-4-yl)-2-[((R)-3-oxo-cyclopentanecarbonyl)-amino]-propionic acid methyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / HCl gas / 20 °C 2: ethyl acetate / 24 h / 20 °C View Scheme

His(1-CH3) (332-80-9) → (S)-3-(1-Methyl-1H-imidazol-4-yl)-2-[((S)-3-oxo-cyclopentanecarbonyl)-amino]-propionic acid methyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / HCl gas / 20 °C 2: ethyl acetate / 24 h / 20 °C View Scheme

His(1-CH3) (332-80-9) → (S)-3-(1-Methyl-1H-imidazol-4-yl)-2-[((R)-3-oxo-cyclopentanecarbonyl)-amino]-propionic acid (406939-49-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / HCl gas / 20 °C 2: ethyl acetate / 24 h / 20 °C 3: 0.5N NaOH / methanol / 0.5 h / 20 °C View Scheme

His(1-CH3) (332-80-9) → (S)-3-(1-Methyl-1H-imidazol-4-yl)-2-[((S)-3-oxo-cyclopentanecarbonyl)-amino]-propionic acid (406939-48-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / HCl gas / 20 °C 2: ethyl acetate / 24 h / 20 °C 3: 0.5N NaOH / methanol / 0.5 h / 20 °C View Scheme

His(1-CH3) (332-80-9) → (S)-1-{(S)-3-(1-Methyl-1H-imidazol-4-yl)-2-[((R)-3-oxo-cyclopentanecarbonyl)-amino]-propionyl}-pyrrolidine-2-carboxylic acid amide

Conditions	Yield
Multi-step reaction with 4 steps 1: 95 percent / HCl gas / 20 °C 2: ethyl acetate / 24 h / 20 °C 3: 0.5N NaOH / methanol / 0.5 h / 20 °C 4: 36 percent / HOBt; DCC / dimethylformamide / 0.8 h / 20 °C View Scheme

His(1-CH3) (332-80-9) → (S)-1-{(S)-3-(1-Methyl-1H-imidazol-4-yl)-2-[((S)-3-oxo-cyclopentanecarbonyl)-amino]-propionyl}-pyrrolidine-2-carboxylic acid amide

Conditions	Yield
Multi-step reaction with 4 steps 1: 95 percent / HCl gas / 20 °C 2: ethyl acetate / 24 h / 20 °C 3: 0.5N NaOH / methanol / 0.5 h / 20 °C 4: 23 percent / HOBt; DCC / dimethylformamide / 0.8 h / 20 °C View Scheme

Upstream product

• 71-00-1 L-histidine 
• 74-88-4 methyl iodide 
• 83471-81-2 (S)-2-Amino-3-{5-[5-((S)-2-amino-2-carboxy-ethyl)-3-methyl-3H-imidazol-4-yldisulfanyl]-1-methyl-1H-imidazol-4-yl}-propionic acid 
• 118891-68-2 N^α-Trityl-N^τ-methyl-L-histidin 
• 124017-72-7 1-methyl<2-(3)H>-L-histidine 
• 79950-65-5 N-[(1,1-dimethylethoxy)carbonyl]-3-[(phenylmethoxy)methyl]-L-histidine 
• 90653-43-3 N(α)-benzyloxycarbonyl-N(?)-t-butoxymethyl-L-histidine methyl ester 
• 99523-88-3 N(α)-benzyloxycarbonyl-N(?)-(2-methoxyethoxy)methyl-L-histidine methyl ester 
• 99523-90-7 N(α)-benzyloxycarbonyl-N(?)-(2-trimethylsilylethoxy)methyl-L-histidine methyl ester 
• 99523-91-8 N(α)-benzyloxycarbonyl-N(τ)-(2-trimethylsilylethoxy)methyl-L-histidine methyl ester 
• 69618-95-7 (S)-7-(methoxycarbonyl)-2-methyl-5-oxo-5,6,7,8-tetrahydroimidazo[1,5-c] pyrimidin-2-ium iodide 
• 90653-42-2 N(α)-benzyloxycarbonyl-N(τ)-tert-butyloxycarbonyl-L-histidine methyl ester 
• 15545-10-5 Z-His-OMe 
• 62982-24-5 L-5-sulfanyl-1-methylhistidine 

Downstream Products

• 57519-09-2 (S)-methyl 2-amino-3-(1-methyl-1H-imidazol-4-yl)propanoate 
• 118891-68-2 N^α-Trityl-N^τ-methyl-L-histidin 

Relevant articles and documents

Immunomodulatory peptides

The invention relates to peptides derivatized with a hydrophilic polymer which, in some embodiments, bind to human FcRn and inhibit binding of the Fc portion of an IgG to an FcRn, thereby modulating serum IgG levels. The disclosed compositions and methods may be used in some embodiments, for example, in treating autoimmune diseases and inflammatory disorders. The invention also relates, in further embodiments, to methods of using and methods of making the peptides of the invention.

Regiospecific alkylation of histidine and histamine at N-1 (τ)

Series of 1-alkyl histidines and histamines have been synthesized by the alkylation of the corresponding 5,6,7,8-tetrahydro-5-oxomidazo[1,5-c]pyrimidines with alkyl halides in aprotic solvents. The method of conversion of the intermediate quaternary salt to the amino acid or amino depends on the nature of the alkyl group.

A Simple Preparation of Nτ-Methyl-L-histidine.

Nτ-Methyl-L-histidine is efficiently prepared in two steps starting from Nα-trityl-L-histidine.