4531-54-8

Basic information

• Product Name: 1H-Imidazol-5-amine,1-methyl-4-nitro-(9CI)
• Synonyms: 1H-Imidazol-5-amine,1-methyl-4-nitro-(9CI);(3-methyl-5-nitro-imidazol-4-yl)amine;3-methyl-5-nitro-imidazol-4-amine;3-methyl-5-nitroimidazol-4-amine;Azathioprine impurity A;Azathioprine Related CoMpound A;1-Methyl-4-nitro-1H-imidazol-5-amine;5-Amino-1-methyl-4-nitroimidazole
• CAS NO: 4531-54-8
• Molecular Formula: C₄H₆N₄O₂
• Molecular Weight: 142.11604
• Product Categories: NITRO
• Mol File: 4531-54-8.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 435 °C at 760 mmHg
• Flash Point: 216.9 °C
• Appearance: /
• Density: 1.67 g/cm³
• Vapor Pressure: 9.04E-08mmHg at 25°C
• Refractive Index: 1.698
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility: DMSO (Slightly, Heated), Methanol (Very Slightly, Heated)
• CAS DataBase Reference: 1H-Imidazol-5-amine,1-methyl-4-nitro-(9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-Imidazol-5-amine,1-methyl-4-nitro-(9CI)(4531-54-8)
• EPA Substance Registry System: 1H-Imidazol-5-amine,1-methyl-4-nitro-(9CI)(4531-54-8)

Safety Data

• Hazardous Substances Data: 4531-54-8(Hazardous Substances Data)

Usage

Uses

5-Amino-1-methyl-4-nitroimidazole is a moiety of Azathioprine (A803350); an immunosuppressive antimetabolite that is also active as a disease modifying antirheumatic drug (DMARD).

InChI:InChI=1/C4H6N4O2/c1-7-2-6-4(3(7)5)8(9)10/h2H,5H2,1H3

Synthetic route

1-methyl-4,5-dinitro-1H-imidazole (19183-15-4) → 1-methyl-4-nitro-1H-imidazol-5-amine (4531-54-8)

Conditions	Yield
With ammonia In water; acetone at 20℃; for 2h; Time;	95.17%

1-methyl-4,5-dinitro-1H-imidazole (19183-15-4) → 1-methyl-4-nitro-1H-imidazol-5-amine (4531-54-8) + 4-amino-1-methyl-5-nitroimidazole (4875-33-6)

Conditions	Yield
With ammonium hydroxide In acetone at 20℃; for 0.5h;	A 95% B 3%

5-chloro-1-methyl-4-nitroimidazole (4897-25-0) → 1-methyl-4-nitro-1H-imidazol-5-amine (4531-54-8)

Conditions	Yield
With ammonia In methanol at 100℃; for 16h; Autoclave;	91%
With ammonium hydroxide In methanol under 6900.69 Torr; for 24h; Autoclave;	19%
With ethanol; ammonia

morpholine (110-91-8) + cyclohexanone (108-94-1) + 5-azido-1-methyl-4-nitro-1H-imidazole (124641-94-7) → 1-methyl-4-nitro-1H-imidazol-5-amine (4531-54-8) + (E)-1-cyclopentyl-N-(1-methyl-4-nitro-1H-imidazol-5-yl)-1-morpholinomethanimine

Conditions	Yield
In methanol at 50℃; for 2h; Mechanism; Solvent; Temperature; Reagent/catalyst; Sealed tube;	A n/a B 89%

1-methyl-4-nitro-1H-imidazole (3034-41-1) → 1-methyl-4-nitro-1H-imidazol-5-amine (4531-54-8)

Conditions	Yield
With trimethylhydrazinium iodide; sodium methylate In dimethyl sulfoxide at 25℃; for 10h;	56%
With trimethylhydrazinium iodide; sodium methylate In dimethyl sulfoxide at 20℃; for 20h;	56%
With N,N-tetramethylene-thiocarbamoyl-sulphenamide	36%

1-methyl-4-nitro-1H-imidazol-5-amine (4531-54-8) + N-(2,6-dichloro-3,5-dimethoxyphenyl)-3-(6-(methylsulfonyl)pyrimidin-4-yl)pyridin-2-amine → 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-(3-methyl-5-nitroimidazol-4-yl)pyrimidin-4-amine

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 40℃; for 12h; Inert atmosphere;	56%

1-methyl-4-nitro-1H-imidazol-5-amine (4531-54-8) → hydroxy-methylamino-acetic acid amide

Conditions	Yield
With hydrogenchloride

1-methyl-4-nitro-1H-imidazol-5-amine (4531-54-8) → 1-methyl-1H-imidazole-4,5-diamine dihydrochloride

Conditions	Yield
With reducing agent In methanol; water under 2250.23 Torr;

Upstream product

• 19183-15-4 1-methyl-4,5-dinitro-1H-imidazole 
• 110-91-8 morpholine 
• 108-94-1 cyclohexanone 
• 124641-94-7 5-azido-1-methyl-4-nitro-1H-imidazole 
• 3034-41-1 1-methyl-4-nitro-1H-imidazole 
• 4897-25-0 5-chloro-1-methyl-4-nitroimidazole 

Relevant articles and documents

Vicarious C-amination of 1-methyl-4-nitroimidazole

A one electron transfer process during the vicarious nucleophilic substitution C-amination of 1-methyl-4-nitroimidazole is detected by EPR-monitoring.

Solvatochromism of heteroaromatic compounds: XIV. 5-Amino-1-methyl-4-nitropyrazole and its analogs

The solvatochromism of H complexes of 5-amino-1-methyl-4-nitropyrazole and 2-nitroaniline derivatives in aprotic protophilic media was described on a quantitative level with the aid of Kamlet-Taft empirical parameters. Specific solvation affects only one of the two long-wave bands, namely that corresponding to an electronic transition involving orbital electron density transfer from the H-bound nitrogen atom. When such transfer does not occur, which is typical of the second transition, specific solvatochromic effect is either weak or absent.

Nucleophilic substitution reactions of 1-methyl-4,5-dinitroimidazole with aqueous ammonia or sodium azide

[Figure not available: see fulltext.] In this work, 5-amino-1-methyl-4-nitroimidazole was synthesized by amination reaction of 1-methyl-4,5-dinitroimidazole with aqueous ammonia in 95% yield. Meanwhile, one of its isomers, 4-amino-1-methyl-5-nitroimidazole as byproduct was obtained from the filtrate. Furthermore, nucleophilic substitution reaction of 1-methyl-4,5-dinitroimidazole with sodium azide gave 5-azido-1-methyl-4-nitroimidazole in 98% yield. The three compounds were characterized by IR, 1H and 13C NMR spectra, melting points, and elemental analysis. The structure of 4-amino-1-methyl-5-nitroimidazole was further confirmed by single crystal X-ray diffraction. These reactions indicate that the nitro group at position 5 of 1-methyl-4,5-dinitroimidazole is quite unstable, as well as partial substitution of nitro group at position 4 also occured in aqueous ammonia. Only one nitro group of the two is involved in nucleophilic substitution reaction in each case.

Method for preparing 1-methyl-5-amino-4-nitroimidazole

The invention belongs to the technical field of preparation of organic intermediates, and particularly relates to a method for preparing 1-methyl-5-amino-4-nitroimidazole. The method takes 1-methyl-4,5-dimetridazloe as a raw material, and the 1-methyl-4,5-dimetridazloe is aminated by ammonia water or ammonia gas to obtain the 1-methyl-5-amino-4-nitroimidazole. The invention provides a brand-new raw material route and a process method for synthesizing the 1-methyl-5-amino-4-nitroimidazole. Reaction is performed at room temperature, and the method has the advantages of gentle conditions, simple process, low cost, high product purity, high yield and the like.