6843-45-4

Basic information

• Product Name: 2,4-Imidazolidinedione, 3-methyl-
• Synonyms: 3-Methylhydantoin;3-Methylimidazolidine-2,4-dione;Hydantoin, 3-methyl-;2,4-Imidazolidinedione, 3-methyl-;3-Methyl-2,4-imidazolidinedione
• CAS NO: 6843-45-4
• Molecular Formula: C₄H₆N₂O₂
• Molecular Weight: 114.1
• Mol File: 6843-45-4.mol
• Article Data: 14

Chemical Properties

• Appearance: /
• Density: 1.285 g/cm³
• CAS DataBase Reference: 2,4-Imidazolidinedione, 3-methyl-(CAS DataBase Reference)
• NIST Chemistry Reference: 2,4-Imidazolidinedione, 3-methyl-(6843-45-4)
• EPA Substance Registry System: 2,4-Imidazolidinedione, 3-methyl-(6843-45-4)

Safety Data

• Hazardous Substances Data: 6843-45-4(Hazardous Substances Data)

Usage

General Description

2,4-Imidazolidinedione, 3-methyl- is a chemical compound also known as 3-Methyl-2,4-imidazolidinedione or 3MI. It is a white crystalline powder and is primarily used in the production of pharmaceuticals and agricultural products. As a heterocyclic compound, it contains a five-membered ring with alternating carbon and nitrogen atoms. 3-Methyl-2,4-imidazolidinedione is also used as a reagent in organic synthesis and as a precursor for the formation of other chemicals. It is important to handle this compound with care as it may cause skin and eye irritation and should be stored and handled in accordance with safety guidelines and regulations.

Synthetic route

ethyl (methylcarbamoyl)glycinate (7150-62-1) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
With sodium methylate In methanol	85%
With hydrogenchloride In ethanol Heating; Yield given;
With sodium hydroxide In water Rate constant; Mechanism; other solvent, other base;
In methanol; water at 25℃; Rate constant; Mechanism; borax buffer (pH = 9.06, ionic strength 0.1), spectrophotometric measured;

methyl {(methylcarbamoyl)amino}acetate (94790-27-9) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
With sodium methylate In methanol	85%
With sodium hydroxide In water Rate constant; Mechanism; other solvent, other base;

2,4-imidazolidinedione (461-72-3) + N,N-dimethylacetamide dimethyl acetal (18871-66-4) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
In toluene Heating;	73%
In toluene for 2h; Reflux;	68%
In toluene for 3h; Heating;	62%
In toluene at 110℃; for 2h;	50%
In toluene at 110℃; for 2h;

2,4-imidazolidinedione (461-72-3) + dimethyl sulfate (77-78-1) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
With sodium hydroxide Heating;	55%
With sodium hydroxide Behandeln mit Salzsaeure unter vermindertem Druck;

Glyoxal (131543-46-9) + N-Methylurea (598-50-5) → 1-methyldiazolidine-2,4-dione (616-04-6) + 1-methylhydantoin (6843-45-4)

Conditions	Yield
With 1-hydroxyethylene-(1,1-diphosphonic acid) In water at 90℃; for 2h; Green chemistry;	A 55% B 25%
Stage #1: Glyoxal With phosphorus pentoxide; water at 20℃; for 0.0833333h; Stage #2: N-Methylurea at 20℃; for 0.166667h;	A 45% B 20%

4-hydroxy-1-methyl-2,5-dioxo-4-imidazolidinecarboxyureide (71886-23-2) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
With hydrogen iodide	52%

2,4-imidazolidinedione (461-72-3) + furan-2,3,5(4H)-trione pyridine (1:1) + dimethyl sulfate (77-78-1) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
Behandeln mit Salzsaeure unter vermindertem Druck;

2,4-imidazolidinedione (461-72-3) + methyl iodide (74-88-4) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
With potassium hydroxide
With potassium tert-butylate In N,N-dimethyl-formamide at 20℃; for 24h; Cooling with ice;	1.01 g

1-methyl-2,5-dioxo-imidazolidine-4-carboxylic acid → 1-methylhydantoin (6843-45-4)

Conditions	Yield
at 190℃;

methyl thioisocyanate (556-61-6) + glycine (56-40-6) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
With potassium hydroxide Behandeln des Reaktionsprodukts mit Quecksilberoxyd anschliessend mit Salzsaeure;

glycine (56-40-6) + N-Methylurea (598-50-5) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
at 130 - 140℃;

2,4-imidazolidinedione (461-72-3) + methyl iodide (74-88-4) → 1-methylhydantoin (6843-45-4) + 1,3-dimethylimidazolidine-2,4-dione (24039-08-5)

Conditions	Yield
With aluminum oxide; potassium fluoride In acetonitrile for 24h; Ambient temperature; Yield given;

2-[(methylcarbamoyl)amino]acetic acid (56099-63-9) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
With trifluoroacetic acid for 1h; Heating;
With sulfuric acid In water at 24.9℃; Rate constant; Mechanism; Thermodynamic data; ΔH(excit); ΔS(excit). Various temperatures, reagents and pH;

1-carbamoyl-3-methylhydantoin (630112-53-7) + hydrogen iodide (10034-85-2) → 1-methylhydantoin (6843-45-4)

3-methyl-5-ureidohydantoin (22494-77-5) + hydrogen iodide (10034-85-2) → 1-methylhydantoin (6843-45-4)

1-(5-methoxy-3-methylhydantoin-5-carbonyl)-3-methylurea (173038-91-0) + hydrogen iodide (10034-85-2) → 1-methylhydantoin (6843-45-4)

5-hydroxy-3-methyl-2,4-dioxo-imidazolidine-1-carboxylic acid nitroamide + hydrogen iodide (10034-85-2) → 1-methylhydantoin (6843-45-4)

3-methyl-5-ethoxy-hydantoin-carboxylic acid-(5)-<α.ω-dimethyl ureide> → 1-methylhydantoin (6843-45-4)

Conditions	Yield
With hydrogen iodide at 130℃;

3-methyl-5-ureido-hydantoin → 1-methylhydantoin (6843-45-4)

Conditions	Yield
With hydrogen iodide

3-methyl-hydantoin-carboxylic acid-(5) → 1-methylhydantoin (6843-45-4)

Conditions	Yield
at 190℃;

9-methyl-uric acid glycol → 1-methylhydantoin (6843-45-4)

Conditions	Yield
With hydrogen iodide

1-carbamoyl-3-methylhydantoin (630112-53-7) + alkaline solution → 1-methylhydantoin (6843-45-4)

Conditions	Yield
Behandeln mit Salzsaeure;

1-carbamoyl-3-methylhydantoin (630112-53-7) + aq. barium hydroxide solution → 1-methylhydantoin (6843-45-4)

Conditions	Yield
Behandeln mit Salzsaeure;

2,4-imidazolidinedione (461-72-3) + methyl iodide (74-88-4) + methanolic KOH-solution → 1-methylhydantoin (6843-45-4)

Conditions	Yield
at 100℃;

1-methyl-3-(1-methyl-2,5-dioxo-imidazolidin-4-yl)-urea (64759-44-0) + hydrogen iodide (10034-85-2) + phosphonium iodide → 1-methylhydantoin (6843-45-4)

3-methyl-2,4-dioxo-imidazolidine-1-carboxylic acid nitroamide + hydrogen iodide (10034-85-2) + phosphonium iodide → 1-methylhydantoin (6843-45-4)

N-(4-ethoxy-1-methyl-2,5-dioxo-imidazolidine-4-carbonyl)-N,N'-dimethyl-urea + hydrogen iodide (10034-85-2) + phosphonium iodide → 1-methylhydantoin (6843-45-4)

Conditions	Yield
at 130℃;

methyl iodide (74-88-4) + silver salt of hydantoin → 1-methylhydantoin (6843-45-4)

Conditions	Yield
at 110 - 120℃; im Rohr;

dimethyl-glycoluril → 1-methyldiazolidine-2,4-dione (616-04-6) + 1-methylhydantoin (6843-45-4)

Conditions	Yield
With hydrogenchloride

1-methylhydantoin (6843-45-4) + indole-2,3-dione (91-56-5) + malononitrile (109-77-3) → (trans-3,7a')-5'-amino-2'-methyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro[indoline-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	95%

furfural (98-01-1) + 1-methylhydantoin (6843-45-4) + malononitrile (109-77-3) → (trans-7,7a)-5-amino-7-(furan-2-yl)-2-methyl-1,3-dioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile

Conditions	Yield
With piperidine In water at 70℃; for 4h;	92%
With piperidine In water at 70℃; diastereoselective reaction;	92%

thiophene-2-carbaldehyde (98-03-3) + 1-methylhydantoin (6843-45-4) + malononitrile (109-77-3) → (trans-7,7a)-5-amino-2-methyl-1,3-dioxo-7-(thiophen-2-yl)-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile

Conditions	Yield
With piperidine In water at 70℃; for 4h;	91%
With piperidine In water at 70℃; diastereoselective reaction;	91%

1-methylhydantoin (6843-45-4) + 4-hydroxy-benzaldehyde (123-08-0) + malononitrile (109-77-3) → (trans-7,7a)-5-amino-7-(4-hydroxyphenyl)-2-methyl-1,3-dioxo-2,3,7,7a-tetrahydro-1Hpyrrolo[1,2-c]imidazole-6-carbonitrile

Conditions	Yield
With piperidine In water at 70℃; for 4h;	91%
With piperidine In water at 70℃; diastereoselective reaction;	91%

1-methylhydantoin (6843-45-4) + 1,5-dimethyl-1H-indole-2,3-dione (66440-60-6) + malononitrile (109-77-3) → (trans-3,7a')-5'-amino-1,2',5-trimethyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro [indoline-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	91%

1-methylhydantoin (6843-45-4) + 4-chlorobenzaldehyde (104-88-1) + malononitrile (109-77-3) → (trans-7,7a)-5-amino-7-(4-chlorophenyl)-2-methyl-1,3-dioxo-2,3,7,7a-tetrahydro-1Hpyrrolo[1,2-c]imidazole-6-carbonitrile

Conditions	Yield
With piperidine In water at 70℃; diastereoselective reaction;	90%
With piperidine In water at 70℃; for 5h;	87%

1-methylhydantoin (6843-45-4) + 4-methyl-benzaldehyde (104-87-0) + malononitrile (109-77-3) → (trans-7,7a)-5-amino-2-methyl-1,3-dioxo-7-(p-tolyl)-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile

Conditions	Yield
With piperidine In water at 70℃; for 4h;	90%
With piperidine In water at 70℃; diastereoselective reaction;	90%

1-methylhydantoin (6843-45-4) + 4-methoxy-benzaldehyde (123-11-5) + malononitrile (109-77-3) → (trans-7,7a)-5-amino-7-(4-methoxyphenyl)-2-methyl-1,3-dioxo-2,3,7,7a-tetrahydro-1Hpyrrolo[1,2-c]imidazole-6-carbonitrile

Conditions	Yield
With piperidine In water at 70℃; for 3.5h;	90%
With piperidine In water at 70℃; diastereoselective reaction;	90%

1-methylhydantoin (6843-45-4) + 5-methyl-indole-2,3-dione (608-05-9) + malononitrile (109-77-3) → (trans-3,7a')-5'-amino-2',5-dimethyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro[indoline-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	90%

1-methylhydantoin (6843-45-4) + 1-methyl-1H-indole-2,3-dione (2058-74-4) + malononitrile (109-77-3) → (trans-3,7a')-5'-amino-1,2'-dimethyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro[indoline-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	90%

1-methylhydantoin (6843-45-4) + 1-allyl-1H-indole-2,3-dione (830-74-0) + malononitrile (109-77-3) → (trans-3,7a')-1-allyl-5'-amino-2'-methyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro-[indoline-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	89%

1-methylhydantoin (6843-45-4) + 5-chloro-1-methylindoline-2, 3-dione (60434-13-1) + malononitrile (109-77-3) → (trans-3,7a')-5'-amino-5-chloro-1,2'-dimethyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro[indoline-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	89%

1-methylhydantoin (6843-45-4) + 5-chloroindole 2,3-dione (17630-76-1) + malononitrile (109-77-3) → (trans-3,7a')-5'-amino-5-chloro-2'-methyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro[indoline-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	88%

1-methylhydantoin (6843-45-4) + 5-fluoro-1-methylisatin (773-91-1) + malononitrile (109-77-3) → (trans-3,7a')-5'-amino-5-fluoro-1,2'-dimethyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro[indoline-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	88%

1-methylhydantoin (6843-45-4) + 5-fluoro-1H-indole-2,3-dione (443-69-6) + malononitrile (109-77-3) → (trans-3,7a')-5'-amino-5-fluoro-2'-methyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro[indo-line-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	87%

7-fluoro-1-methyl-1H-indole-2,3-dione (875003-43-3) + 1-methylhydantoin (6843-45-4) + malononitrile (109-77-3) → (cis-3,7a')-5'-amino-7-fluoro-1,2'-dimethyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro[indoline-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	87%

1-methylhydantoin (6843-45-4) → N,N`-dimethylethylenediamine (110-70-3)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 72h; Heating; Argon;	85%

1-methylhydantoin (6843-45-4) + 2-chloro-benzaldehyde (89-98-5) → 5-[1-(2-chlorophenyl)methylidene]-3-methylimidazolidine-2,4-dione (88568-75-6)

Conditions	Yield
With potassium acetate; acetic anhydride In acetic acid for 16h; Heating;	85%

1-methylhydantoin (6843-45-4) + 5-Bromo-1H-indole-2,3-dione (87-48-9) + malononitrile (109-77-3) → (trans-3,7a')-5'-amino-5-bromo-2'-methyl-1',2,3'-trioxo-1',2',3',7a'-tetrahydrospiro [indoline-3,7'-pyrrolo[1,2-c]imidazole]-6'-carbonitrile

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	81%

1-methylhydantoin (6843-45-4) + 4-bromo-benzaldehyde (1122-91-4) + malononitrile (109-77-3) → (trans-7,7a)-5-amino-7-(4-bromophenyl)-2-methyl-1,3-dioxo-2,3,7,7a-tetrahydro-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile

Conditions	Yield
With piperidine In water at 70℃; for 4h;	80%
With piperidine In water at 70℃; diastereoselective reaction;	80%

1-methylhydantoin (6843-45-4) + 5-iodoisatin (20780-76-1) + malononitrile (109-77-3) → C15H10IN5O3

Conditions	Yield
With piperidine In water at 80℃; diastereoselective reaction;	80%

1-methylhydantoin (6843-45-4) + 7-bromo-1 H-indole-3-carbaldehyde (115666-21-2) → 5-((7-bromo-1H-indol-3-yl)methylene)-3-methylimidazolidine-2,4-dione

Conditions	Yield
With piperidine at 110℃; for 6h; Sealed tube;	73%

1-methylhydantoin (6843-45-4) + Indole-3-carboxaldehyde (487-89-8) → 5-(1H-Indol-3-ylmethylene)-3-methylimidazolidine-2,4-dione (200804-97-3)

Conditions	Yield
In piperidine at 110℃; for 4h;	71%

1-methylhydantoin (6843-45-4) + 4-(7-(cyclopropylamino)-3-formylpyrazolo[1,5-a]pyrimidin-5-ylamino)benzonitrile → (Z)-4-(7-(cyclopropylamino)-3-((1-methyl-2,5-dioxoimidazolidin-4-ylidene)methyl)pyrazolo[1,5-a]pyrimidin-5-ylamino)benzonitrile

Conditions	Yield
With piperidine In ethanol at 80℃; for 15h;	68%
With piperidine In ethanol at 80℃; for 15h;	68%

1-methylhydantoin (6843-45-4) + 2-chloro-benzaldehyde (89-98-5) → 5-[2-chlorophenyl(hydroxy)methyl]-3-methylimidazolidine-2,4-dione (947396-30-7)

Conditions	Yield
With potassium acetate; acetic anhydride In acetic acid for 8h; Heating;	67%

1-methylhydantoin (6843-45-4) + tert-Butyldimethyl(prop-2-ynyloxy)silane (76782-82-6) → 5-[3-(tert-butyl-dimethyl-silanyloxy)-prop-1-ynyl]-1-methyl-1,3-dihydro-imidazol-2-one (766549-73-9)

Conditions	Yield
Stage #1: 1-methylhydantoin; tert-Butyldimethyl(prop-2-ynyloxy)silane With butyl magnesium bromide In tetrahydrofuran Stage #2: With toluene-4-sulfonic acid In chloroform Further stages.;	62%

Upstream product

• 461-72-3 2,4-imidazolidinedione 
• 77-78-1 dimethyl sulfate 
• 74-88-4 methyl iodide 
• 56-40-6 glycine 
• 598-50-5 N-Methylurea 
• 56099-63-9 2-[(methylcarbamoyl)amino]acetic acid 
• 18871-66-4 N,N-dimethylacetamide dimethyl acetal 
• 131543-46-9 Glyoxal 
• 22494-77-5 3-methyl-5-ureidohydantoin 
• 876479-91-3 5-hydroxy-3-methyl-2,4-dioxo-imidazolidine-1-carboxylic acid amide 
• 10034-85-2 hydrogen iodide 
• 3659-97-0 1-methylparabanic acid 
• 7647-01-0 hydrogenchloride 
• 3720-98-7 1,6-dimethyltetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)dione 

Downstream Products

• 630112-53-7 1-carbamoyl-3-methylhydantoin 
• 99973-29-2 3-methyl-5-(2-nitro-benzylidene)-imidazolidine-2,4-dione 
• 110-70-3 N,N`-dimethylethylenediamine 
• 947396-30-7 5-[2-chlorophenyl(hydroxy)methyl]-3-methylimidazolidine-2,4-dione 
• 88568-75-6 5-[1-(2-chlorophenyl)methylidene]-3-methylimidazolidine-2,4-dione 
• 109754-09-8 5-benzylidene-3-methyl-imidazolidine-2,4-dione 
• 1408245-11-3 1-{4-[4-bromo-1-(2-methylpropyl)-1H-benzotriazol-5-yl]benzyl}-3-methylimidazolidine-2,4-dione 
• 1295301-38-0 3-methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)imidazolidine-2,4-dione 
• 1408003-11-1 1-({4-[4-chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]cyclohex-3-en-1-yl}methyl)-3-methylimidazolidine-2,4-dione 

Relevant articles and documents

-

-

2,4-Imidazolinedione heterocyclic derivative, and preparation method and use thereof

The invention belongs to the field of chemical medicines, and concretely relates to a 2,4-imidazolinedione heterocyclic derivative, and a preparation method and a use thereof. The structure of the 2,4-imidazolinedione heterocyclic derivative is represented by formula I. The invention also provides the preparation method and the use of the 2,4-imidazolinedione heterocyclic derivative. The 2,4-imidazolinedione heterocyclic derivative has a good inhibition effect on Pim-1 protein kinase micro-molecules, and has important exploitation application prospect.

NOVEL AMIDE DERIVATIVE AND USE THEREOF AS MEDICINE

Provided are a novel low-molecular-weight compound that suppresses production of induction type MMPs, particularly MMP-9, rather than production of hemostatic type MMP-2, as well as a prophylactic/therapeutic drug for autoimmune diseases or osteoarthritis. An amide derivative represented by the following formula (I) wherein each symbol is as defined in the specification, or a pharmacologically acceptable salt thereof.