71510-95-7

Basic information

• Product Name: Ethyl-N-methyl malonamide
• Synonyms: Ethyl 3-(methylamino)-3-oxopropanoate;N-METHYL-MALONAMIC ACID ETHYL ESTER;3-(Methylamino)-3-oxo-propanoic acid ethyl ester;ETHYL 1-METHYL AMIDOMALONATE;ETHYL-N-METHYLAMIDOMALONATE;ETHYL-N-METHYL MALONAMIDE;Ethyl-N-methyl;Monoethyl malonate formamide
• CAS NO: 71510-95-7
• Molecular Formula: C₆H₁₁NO₃
• Molecular Weight: 144.17
• Product Categories: Pharmaceutical Intermediates
• Mol File: 71510-95-7.mol
• Article Data: 5

Chemical Properties

• Melting Point: 34-35 °C(Solv: cyclohexane (110-82-7))
• Boiling Point: 286.5 °C at 760 mmHg
• Flash Point: 127.1 °C
• Appearance: /
• Density: 1.059 g/cm³
• Vapor Pressure: 0.00263mmHg at 25°C
• Refractive Index: 1.428
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Sparingly), DMSO (Slightly), Methanol (Very Slightly)
• PKA: 13.94±0.46(Predicted)
• CAS DataBase Reference: Ethyl-N-methyl malonamide(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl-N-methyl malonamide(71510-95-7)
• EPA Substance Registry System: Ethyl-N-methyl malonamide(71510-95-7)

Safety Data

• Hazardous Substances Data: 71510-95-7(Hazardous Substances Data)

Usage

General Description

Ethyl-N-methyl malonamide is a chemical compound that is often used as a reagent in organic synthesis. It is a derivative of malonic acid and contains an ethyl and a methyl group attached to the nitrogen atom. Ethyl-N-methyl malonamide has been found to be an effective ligand in the synthesis of coordination complexes and can also be used as a precursor for the synthesis of pharmaceuticals, agrochemicals, and other organic compounds. Ethyl-N-methyl malonamide is a versatile compound with a wide range of potential applications in the field of organic chemistry.

InChI:InChI=1/C6H11NO3/c1-3-10-6(9)4-5(8)7-2/h3-4H2,1-2H3,(H,7,8)

Synthetic route

2-carboethoxy-N-methyl-acetamide (71510-95-7) + C14H13FN2O → (3S,4R)-3-ethoxycarbonyl-4-(4-fluorophenyl)-N-methylpiperidine-2,6-dione (188302-25-2)

Conditions	Yield
Stage #1: C14H13FN2O With C31H44N4O4; ytterbium(III) triflate In dichloromethane at 35℃; for 0.5h; Molecular sieve; Inert atmosphere; Stage #2: 2-carboethoxy-N-methyl-acetamide With triethylamine In dichloromethane at 40℃; for 72h; Reagent/catalyst; Solvent; Concentration; Inert atmosphere; Molecular sieve; stereoselective reaction;	90%

2-carboethoxy-N-methyl-acetamide (71510-95-7) + p-fluorocinnamoyl-3,5-dimethyl-1H-pyrazole → (3R,4S)-3-ethoxycarbonyl-4-(4-fluorophenyl)-N-methylpiperidine-2,6-dione

Conditions	Yield
Stage #1: 2-carboethoxy-N-methyl-acetamide; p-fluorocinnamoyl-3,5-dimethyl-1H-pyrazole With C32H46N4O4; ytterbium(III) triflate In toluene at 35℃; for 0.333333h; Stage #2: With triethylamine In toluene at 30 - 50℃; Reagent/catalyst; Solvent;	85.5%

2-carboethoxy-N-methyl-acetamide (71510-95-7) → 2-carboisopropoxy-N-methyl-acetamide (323203-14-1)

Conditions	Yield
In isopropyl alcohol; mineral oil	82%
In isopropyl alcohol; mineral oil	82%

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 3-[3-(4-fluorophenyl)acryloyl]-(R)-4-phenyl-oxazolidin-2-one → (3S,4R)-3-ethoxycarbonyl-4-(4-fluorophenyl)-N-methylpiperidine-2,6-dione (188302-25-2)

Conditions	Yield
Stage #1: 2-carboethoxy-N-methyl-acetamide With sodium hydride In dimethyl sulfoxide at 20℃; Inert atmosphere; Stage #2: 3-[3-(4-fluorophenyl)acryloyl]-(R)-4-phenyl-oxazolidin-2-one In dimethyl sulfoxide at 20℃; Inert atmosphere;	80%

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 4-nitrophenyl 3-phenylprop-2-ynoate → (Z)-ethyl 5-benzylidene-2-(methylamino)-4-oxo-4,5-dihydrofuran-3-carboxylate

Conditions	Yield
With 1,3-bis(mesityl)imidazolium chloride; N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at 65℃; for 10h; Reagent/catalyst; Molecular sieve; Inert atmosphere; regioselective reaction;	77%

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 1,2-diamino-benzene (95-54-5) → 4-Methylamino-1,3-dihydro-benzo[b][1,4]diazepin-2-one (91598-13-9)

Conditions	Yield
With trichlorophosphate at 110℃; for 4h;	59.1%

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 1,2,4-triaminopyridin-1-ium 2,4,6-trimethylbenzenesulfonate → 2-(7-amino-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-N-methylacetamide

Conditions	Yield
With sodium hydroxide In methanol Reflux;	39.4%

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 1,2,4-triamino-4-bromopyridin-1-ium-2,4,6-trimethylbenzenesulfonate → 2-(7-amino-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-N-methylacetamide

Conditions	Yield
With sodium hydroxide In methanol Reflux;	39.4%

2-carboethoxy-N-methyl-acetamide (71510-95-7) → ethyl 2-bromo-3-(methylamino)-3-oxopropanoate

Conditions	Yield
With sodium hydrogen sulfate; N-Bromosuccinimide In tetrahydrofuran at 0℃; Inert atmosphere;	20%

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 4-fluorobenzaldehyde (459-57-4) → trans 3-ethoxycarbonyl-4-(4'-fluorophenyl)-N-methyl-piperidine-2,6-dione (202534-94-9)

Conditions	Yield
With sodium methylate; acetic acid In water; ethyl acetate
With sodium methylate; acetic acid In water; ethyl acetate

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 3-phenyl-propenal (104-55-2) → C15H19NO4 + C15H19NO4 (323203-12-9)

Conditions	Yield
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; potassium acetate In 2,2,2-trifluoroethanol at 20℃; optical yield given as %ee; enantioselective reaction;

(E)-3-phenylpropenal (14371-10-9) + 2-carboethoxy-N-methyl-acetamide (71510-95-7) → (3R,4S,6S)-ethyl 6-hydroxy-1-methyl-2-oxo-4-phenylpiperidine-3-carboxylate

Conditions	Yield
With (R)-2-(diphenyl(trimethylsilyloxy)methyl)pyrrolidine; potassium acetate In 2,2,2-trifluoroethanol at 20℃; for 14h; optical yield given as %ee; enantioselective reaction;

3-(4-nitrophenyl)-propenal (49678-08-2) + 2-carboethoxy-N-methyl-acetamide (71510-95-7) → (3S,4R,6R)-ethyl 6-hydroxy-1-methyl-4-(4-nitrophenyl)-2-oxopiperidine-3-carboxylate (1345157-71-2)

Conditions	Yield
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; potassium acetate In 2,2,2-trifluoroethanol at 20℃; for 14h; optical yield given as %ee; enantioselective reaction;

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 4-chlorocinnamaldehyde (1075-77-0) → (3S,4R,6R)-ethyl 4-(4-chlorophenyl)-6-hydroxy-1-methyl-2-oxopiperidine-3-carboxylate (1345157-65-4) + ethyl 4-(4-chlorophenyl)-6-hydroxy-1-methyl-2-oxopiperidine-3-carboxylate

Conditions	Yield
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; potassium acetate In 2,2,2-trifluoroethanol at 20℃; for 14h; optical yield given as %de; enantioselective reaction;

2-carboethoxy-N-methyl-acetamide (71510-95-7) + trans-4-bromocinnamaldehyde (49678-04-8) → (3S,4R,6R)-ethyl 4-(4-bromophenyl)-6-hydroxy-1-methyl-2-oxopiperidine-3-carboxylate (1345157-68-7) + ethyl 4-(4-bromophenyl)-6-hydroxy-1-methyl-2-oxopiperidine-3-carboxylate

Conditions	Yield
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; potassium acetate In 2,2,2-trifluoroethanol at 20℃; for 14h; optical yield given as %de; enantioselective reaction;

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 3-(4-fluoro-phenyl)-propenal (51791-26-5, 24654-55-5) → ethyl 4-(4-fluorophenyl)-6-hydroxy-1-methyl-2-oxopiperidine-3-carboxylate + ethyl 4-(4-fluorophenyl)-6-hydroxy-1-methyl-2-oxopiperidine-3-carboxylate

Conditions	Yield
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; potassium acetate In 2,2,2-trifluoroethanol at 20℃; for 14h; optical yield given as %de; enantioselective reaction;

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 3-(4-methylphenyl)acrylaldehyde (1504-75-2) → (3S,4R,6R)-ethyl 6-hydroxy-1-methyl-2-oxo-4-p-tolylpiperidine-3-carboxylate (1345157-60-9) + ethyl 6-hydroxy-1-methyl-2-oxo-4-p-tolylpiperidine-3-carboxylate

Conditions	Yield
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; potassium acetate In 2,2,2-trifluoroethanol at 20℃; for 14h; optical yield given as %de; enantioselective reaction;

2-carboethoxy-N-methyl-acetamide (71510-95-7) + p-fluorocinnamoyl-3,5-dimethyl-1H-pyrazole → (3S,4R)-3-ethoxycarbonyl-4-(4-fluorophenyl)-N-methylpiperidine-2,6-dione (188302-25-2)

Conditions	Yield
Stage #1: 2-carboethoxy-N-methyl-acetamide; p-fluorocinnamoyl-3,5-dimethyl-1H-pyrazole With C32H46N4O4; ytterbium(III) triflate In dichloromethane at 35℃; for 0.333333h; Stage #2: With triethylamine In dichloromethane at 30 - 50℃; Reagent/catalyst;	51 g

2-carboethoxy-N-methyl-acetamide (71510-95-7) + C14H14N2O (37612-74-1) → C15H17NO4 + (3R,4S)-3-ethoxycarbonyl-4-(4-phenyl)-N-methylpiperidine-2,6-dione

Conditions	Yield
With C31H44N4O4; triethylamine; ytterbium(III) triflate In 1,2-dichloro-ethane at 40℃; for 72h; Molecular sieve; Inert atmosphere; Overall yield = 87 %; stereoselective reaction;	A n/a B n/a

2-carboethoxy-N-methyl-acetamide (71510-95-7) + C14H13FN2O → (3R,4S)-3-ethoxycarbonyl-4-(4-fluorophenyl)-N-methylpiperidine-2,6-dione + (3S,4R)-3-ethoxycarbonyl-4-(4-fluorophenyl)-N-methylpiperidine-2,6-dione (188302-25-2) + C15H16FNO4

Conditions	Yield
With (2S,2'S)-1,1'-(propane-1,3-diyl)bis(N-(2,6-dimethylphenyl)pyrrolidine-2-carboxamide)-N,N'-dioxide; triethylamine; ytterbium(III) triflate In dichloromethane at 35℃; for 72h; Inert atmosphere; Overall yield = 10 %;	A n/a B n/a C n/a

2-carboethoxy-N-methyl-acetamide (71510-95-7) + C14H13FN2O → (3S,4R)-3-ethoxycarbonyl-4-(4-fluorophenyl)-N-methylpiperidine-2,6-dione (188302-25-2) + C15H16FNO4

Conditions	Yield
With C35H52N4O4; triethylamine; ytterbium(III) triflate In dichloromethane at 35℃; for 72h; Inert atmosphere; Overall yield = 9 %;	A n/a B n/a

2-carboethoxy-N-methyl-acetamide (71510-95-7) + C14H13FN2O → trans 3-ethoxycarbonyl-4-(4'-fluorophenyl)-N-methyl-piperidine-2,6-dione (202534-94-9)

Conditions	Yield
Stage #1: 2-carboethoxy-N-methyl-acetamide With potassium tert-butylate In dichloromethane at 20℃; for 0.333333h; Inert atmosphere; Stage #2: C14H13FN2O In dichloromethane at 20℃; for 24h; Inert atmosphere;

2-carboethoxy-N-methyl-acetamide (71510-95-7) + 3,5-dimethyl-1-[3-(4-chlorophenyl)propanonyl]pyrazole → C15H16ClNO4 + (3R,4S)-3-ethoxycarbonyl-4-(4-chlorophenyl)-N-methylpiperidine-2,6-dione

Conditions	Yield
With C31H44N4O4; triethylamine; ytterbium(III) triflate In 1,2-dichloro-ethane at 40℃; for 72h; Molecular sieve; Inert atmosphere; Overall yield = 92 %; stereoselective reaction;	A n/a B n/a

methyl-propanedioic acid (516-05-2) + 2-carboethoxy-N-methyl-acetamide (71510-95-7) → ethyl 1,5-dimethyl-2,4,6-pyridin-3-carboxylate

Conditions	Yield
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide; toluene at 20 - 35℃; for 56h; Temperature;

Upstream product

• 36239-09-5 ethyl chlorocarbonylacetate 
• 74-89-5 methylamine 
• 19172-47-5 Lawessons reagent 
• 156025-63-7 N-hydroxy-N-methyl-2-carbetoxyethanamide 
• 593-51-1 methylamine hydrochloride 
• 105-53-3 diethyl malonate 

Downstream Products

• 109887-52-7 (3R,4S)-3-ethoxycarbonyl-4-(4-fluorophenyl)-N-methylpiperidine-2,6-dione 
• 188302-25-2 (3S,4R)-3-ethoxycarbonyl-4-(4-fluorophenyl)-N-methylpiperidine-2,6-dione 
• 109887-52-7 C₁₅H₁₆FNO₄ 
• 202534-94-9 trans 3-ethoxycarbonyl-4-(4'-fluorophenyl)-N-methyl-piperidine-2,6-dione 

Relevant articles and documents

Asymmetric Synthesis of α,β-Epoxy-?-lactams through Tandem Darzens/Hemiaminalization Reaction

A catalytic asymmetric tandem Darzens/hemiaminalization reaction of glyoxals with α-bromo-β-esteramides or α-bromo-β-ketoamide was accomplished in the presence of a chiral N,N′-dioxide/Yb(III) complex. Various chiral α,β-epoxy-?-lactams were obtained in moderate to good yields with excellent diastereo- and enantioselectivities. The versatility of the transformation is illustrated in the formal synthesis of berkeleyamide D.

SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE

The present invention provides novel heteroaryl compounds, pharmaceutical acceptable salts and formulations thereof. They are useful in preventing, managing, treating or lessening the severity of a protein kinase-mediated disease. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of protein kinase-mediated disease.

DIHYDROPYRIDINONE DERIVATIVES

The invention relates to novel dihydropyridinone derivatives, processes for their preparation, and their use in medicaments, especially for the treatment of chronic obstructive pulmonary diseases, acute coronary syndrome, acute myocardial infarction and heart failure development.