188612-53-5

Basic information

• Product Name: 5-(Amino-1-(N-methyl Carbamoyl)
• Synonyms: 5-(Amino-1-(N-methyl Carbamoyl);5-Amino-1-(N-methylcarbamoyl)imidazole-4-carboxamide;Temozolomide Impurity 3
• CAS NO: 188612-53-5
• Molecular Formula: C₆H₉N₅O₂
• Molecular Weight: 183.16796
• Mol File: 188612-53-5.mol
• Article Data: 11

Chemical Properties

• Melting Point: 170 °C (decomp)
• Appearance: /
• Density: 1.69±0.1 g/cm3(Predicted)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: DMSO (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly, Sonicated)
• PKA: 13.48±0.46(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: 5-(Amino-1-(N-methyl Carbamoyl)(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(Amino-1-(N-methyl Carbamoyl)(188612-53-5)
• EPA Substance Registry System: 5-(Amino-1-(N-methyl Carbamoyl)(188612-53-5)

Safety Data

• Hazardous Substances Data: 188612-53-5(Hazardous Substances Data)

Usage

Description

5-(Amino-1-(N-methyl Carbamoyl), also known as 5-Amino-N1-methyl-1H-imidazole-1,4-dicarboxamide, is a metabolite of Temozolomide (T017775), an imidazotetrazine alkylating agent and antineoplastic. It plays a significant role in the pharmaceutical industry due to its association with cancer treatment.

Uses

Used in Pharmaceutical Industry:
5-(Amino-1-(N-methyl Carbamoyl) is used as a metabolite for [application reason] in the pharmaceutical industry. It is derived from Temozolomide, an antineoplastic agent, which makes it a crucial component in the development and understanding of cancer treatment.
Used in Anticancer Applications:
In the field of oncology, 5-(Amino-1-(N-methyl Carbamoyl) is used as a metabolite for enhancing the effectiveness of cancer treatment. Its connection to Temozolomide, an alkylating agent, allows it to contribute to the inhibition of tumor growth and the progression of cancer.
Used in Research and Development:
5-(Amino-1-(N-methyl Carbamoyl) is also used as a research compound for further investigation into its potential applications and interactions with other pharmaceutical compounds. This research can lead to the development of new drugs and therapies for various types of cancer.

Synthetic route

5-Aminoimidazole-4-carboxamide (360-97-4) + methylcarbamoyl chloride (6452-47-7) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
With triethylamine In acetonitrile at -5 - 20℃; for 3h; Temperature;	92.6%

1-methyl-3-methylcarbamoyliminomethyl urea (65906-68-5) + 2-Amino-2-cyanoacetamide (6719-21-7) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
With hydrogenchloride In water; acetonitrile at 20 - 25℃; for 24h; Solvent; Reagent/catalyst;	90.5%
With acetic acid In methanol at 20 - 25℃; for 18h;	88.04%

5-amino-1H-imidazole-4-carboxamide monohydrochloride (72-40-2) + methyl isocyanate (624-83-9) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
With triethylamine In dimethyl sulfoxide at 20℃;	90%
With triethylamine In dimethyl sulfoxide at 25℃;	85%
With triethylamine 1.) CH3CN, 25 deg C, 10 min, 2.) 25 deg C, 18 h; Yield given. Multistep reaction;

2,5-dioxopyrrolidin-1-yl methylcarbamate (18342-66-0) + 5-Aminoimidazole-4-carboxamide (360-97-4) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 0 - 25℃; for 17h;	88%

methylamine (74-89-5) + 5-Amino-4-carbamoyl-imidazole-1-carboxylic acid 4-nitro-phenyl ester (196806-10-7) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
In tetrahydrofuran at 25℃; for 5h;	87%
In tetrahydrofuran; ethanol at 25℃;	48%

5-Aminoimidazole-4-carboxamide (360-97-4) + imidazole-1-carboxylic acid N-methylamide (72002-25-6) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
In acetonitrile at 55 - 60℃; for 6h; Solvent;	80%

5-Aminoimidazole-4-carboxamide (360-97-4) + methylcarbamoyl chloride (6452-47-7) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
With triethylamine In acetonitrile at -5 - 20℃; for 3h; Temperature;	92.6%

1-methyl-3-methylcarbamoyliminomethyl urea (65906-68-5) + 2-Amino-2-cyanoacetamide (6719-21-7) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
With hydrogenchloride In water; acetonitrile at 20 - 25℃; for 24h; Solvent; Reagent/catalyst;	90.5%
With acetic acid In methanol at 20 - 25℃; for 18h;	88.04%

5-amino-1H-imidazole-4-carboxamide monohydrochloride (72-40-2) + methyl isocyanate (624-83-9) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
With triethylamine In dimethyl sulfoxide at 20℃;	90%
With triethylamine In dimethyl sulfoxide at 25℃;	85%
With triethylamine 1.) CH3CN, 25 deg C, 10 min, 2.) 25 deg C, 18 h; Yield given. Multistep reaction;

2,5-dioxopyrrolidin-1-yl methylcarbamate (18342-66-0) + 5-Aminoimidazole-4-carboxamide (360-97-4) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 0 - 25℃; for 17h;	88%

methylamine (74-89-5) + 5-Amino-4-carbamoyl-imidazole-1-carboxylic acid 4-nitro-phenyl ester (196806-10-7) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
In tetrahydrofuran at 25℃; for 5h;	87%
In tetrahydrofuran; ethanol at 25℃;	48%

5-Aminoimidazole-4-carboxamide (360-97-4) + imidazole-1-carboxylic acid N-methylamide (72002-25-6) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
In acetonitrile at 55 - 60℃; for 6h; Solvent;	80%

5-amino-1H-imidazole-4-carboxamide monohydrochloride (72-40-2) + methylcarbamoyl chloride (6452-47-7) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
With triethylamine 1.) CH3CN, 25 deg C, 15 min, 2.) CH3CN, 2 h; Yield given. Multistep reaction;

1,1'-carbonyldiimidazole (530-62-1) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetonitrile; N,N-dimethyl-formamide / 2 h / 20 °C 2: acetonitrile / 6 h / 55 - 60 °C View Scheme

4-nitrophenyl N-methylcarbamate (5819-21-6) + 5-amino-1H-imidazole-4-carboxamide monohydrochloride (72-40-2) → 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5)

Conditions	Yield
Stage #1: 5-amino-1H-imidazole-4-carboxamide monohydrochloride With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 0.166667h; Stage #2: 4-nitrophenyl N-methylcarbamate In acetonitrile at 20℃; for 24h;	10 g

5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5) → temozolomide (85622-93-1)

Conditions	Yield
Stage #1: 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide With lithium chloride hydrate; acetic acid In water at 20℃; for 0.5h; Stage #2: With iodine; sodium nitrite In water at -10 - 20℃; for 3h;	76%
Stage #1: 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide With acetic acid; lithium bromide In water at 20℃; for 1h; Stage #2: With sodium nitrite In water at -10 - 20℃; for 6h; Stage #3: With sodium thiosulfate In water for 0.333333h; Product distribution / selectivity;	64%
Stage #1: 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide With sodium nitrite In water at 0℃; for 0.333333h; Stage #2: With tartaric acid In water at 0 - 60℃; for 4h;	47%

orthoformic acid triethyl ester (122-51-0) + 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5) → temozolomide

Conditions	Yield
In dimethyl sulfoxide at 40 - 50℃; for 60h;	40%

triethoxymethylbenzene (1663-61-2) + 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5) → 3-Methyl-4-oxo-2-phenyl-3,4-dihydro-imidazo[1,5-a][1,3,5]triazine-8-carboxylic acid amide

Conditions	Yield
In dimethyl sulfoxide at 80 - 100℃; for 60h;	40%

5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5) → temozolomide (85622-93-1) + 2-Azahypoxanthine (4656-86-4)

Conditions	Yield
With hydrogenchloride; sodium nitrite at 5 - 25℃;	A 35% B 15%

orthoformic acid triethyl ester (122-51-0) + 5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5) → 5-ethoxymethyleneimino-1-(N-methylcarbamoyl)imidazole-4-carboxamide

Conditions	Yield
In dimethyl sulfoxide at 50℃; for 20h;	20%

5-amino-N1-methyl-1H-imidazole-1,4-dicarboxamide (188612-53-5) → temozolomide (85622-93-1) + 9-(N-methylcarbamoyl)-2-azahypoxanthine

Conditions	Yield
With tartaric acid; sodium nitrite In water at 0℃; for 1h;	A 45 % Chromat. B n/a

Upstream product

• 72-40-2 5-amino-1H-imidazole-4-carboxamide monohydrochloride 
• 624-83-9 methyl isocyanate 
• 6452-47-7 methylcarbamoyl chloride 
• 74-89-5 methylamine 
• 196806-10-7 5-Amino-4-carbamoyl-imidazole-1-carboxylic acid 4-nitro-phenyl ester 
• 18342-66-0 2,5-dioxopyrrolidin-1-yl methylcarbamate 
• 360-97-4 5-Aminoimidazole-4-carboxamide 
• 65906-68-5 1-methyl-3-methylcarbamoyliminomethyl urea 
• 6719-21-7 2-Amino-2-cyanoacetamide 
• 530-62-1 1,1'-carbonyldiimidazole 
• 72002-25-6 imidazole-1-carboxylic acid N-methylamide 
• 5819-21-6 4-nitrophenyl N-methylcarbamate 

Downstream Products

• 85622-93-1 temozolomide 
• 4656-86-4 2-azohypoxanthine 

Relevant articles and documents

PROCESS FOR PREPARING HIGHLY PURE TEMOZOLOMIDE

The present invention provides a commercially viable process for preparation of highly pure Temozolomide (VI), which is useful in the treatment of cancer. The invention also provides an economically viable process for an intermediate compound of formula III useful in the process for preparing Temozolomide.

TEMOZOLOMIDE PROCESS

The present invention relates to improved process for the preparation of Temozolomide Formula I. Said Temozolomide (I) is useful in the treatment of cancer.

A tiemoazoleamine and method for synthesizing intermediate

The invention discloses a modified optimized synthetic method for temozolomide and an intermediate thereof. The synthetic method is characterized in that a new oxidation ring-closing reagent is introduced for a reaction with lithium chloride and sodium nitrite in an aqueous solution, and the synthetic method helps to improve the yield of the reaction, increase the controllability on the reaction and avoid usage of methyl isocyanate with relatively high toxicity.