25717-80-0

Basic information

• Product Name: Molsidomine
• Synonyms: ethyl (3-morpholin-4-yl-1-oxa-2-aza-3-azoniacyclopenta-2,4-dien-5-yl)aminoformate;CORVATON;corvasal;molsidolat;morial;n-(ethoxycarbonyl)-3-(4-morpholinyl)-sydnoneimin;n-carboxy-3-morpholino-sydnoneiminethylester;n-carboxy-3-morpholinosydnonimineethylester
• CAS NO: 25717-80-0
• Molecular Formula: C₉H₁₄N₄O₄
• Molecular Weight: 242.23
• EINECS: 247-207-4
• Product Categories: Nitric Oxide;API
• Mol File: 25717-80-0.mol

Chemical Properties

• Melting Point: 140-141°C
• Boiling Point: 385.05°C (rough estimate)
• Appearance: colorless or white crystalline powder
• Density: 1.3186 (rough estimate)
• Refractive Index: 1.6300 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Sparingly soluble in water, soluble in anhydrous ethanol and in methylene chloride.
• PKA: pK (100°) 3.0 ± 0.1
• Merck: 14,6234
• CAS DataBase Reference: Molsidomine(CAS DataBase Reference)
• NIST Chemistry Reference: Molsidomine(25717-80-0)
• EPA Substance Registry System: Molsidomine(25717-80-0)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 36
• WGK Germany: 3
• RTECS: WU7677400
• Hazardous Substances Data: 25717-80-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Molsidomine is used as an antianginal agent for the treatment of angina pectoris. As a therapeutic agent, it helps in managing chest pain and discomfort caused by insufficient blood flow to the heart muscles. Its action as a direct nitric oxide donor contributes to its effectiveness in treating this condition.

Originator

Corvasal,Hoechst

Manufacturing Process

1.6 parts by volume of ethyl chloroformate is stirred dropwise into a suspension of 1.0 part by weight of 3-morpholinosydnonimine hydrochloride in 5 parts by volume of pyridine, and the mixture is agitated for a while to allow reaction to take place. Pyridine is removed from the reaction mixture by evaporation, and the residue is dissolved in a small amount of water and extracted with chloroform several times. The extract is dehydrated by adding anhydrous magnesium sulfate and subjected to filtration. Chloroform is removed from the filtrate by distillation, crude crystals being obtained. Recrystallization of the crude crystals from toluene gives 0.6 part by weight of 3-morpholino-N-carboethoxysydnonimine having a melting point of 140°- 141°C. Yield 51%.

Therapeutic Function

Coronary vasodilator

InChI:InChI=1/C9H14N4O4/c1-2-16-9(14)10-8-7-13(11-17-8)12-3-5-15-6-4-12/h7H,2-6H2,1H3

Synthetic route

4-lithiomolsidomine → molsidomine (25717-80-0)

Conditions	Yield
With water	100%

chloroformic acid ethyl ester (541-41-3) + Linsidomine hydrochloride (16142-27-1) → molsidomine (25717-80-0)

Conditions	Yield
With sodium hydrogencarbonate

molsidomine (25717-80-0) → 4-lithiomolsidomine

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran; tetrahydrofuran-d8 Inert atmosphere;	100%

sulfur (10544-50-0) + molsidomine (25717-80-0) + mercury dichloride → bis((6-ethoxycarbonyl-3-morpholinyl-sydnone imine-4-yl)thio)mercury(II)

Conditions	Yield
Stage #1: molsidomine With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: sulfur In tetrahydrofuran at 0℃; Inert atmosphere; Stage #3: mercury dichloride In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	88%

triphenylborane (960-71-4) + molsidomine (25717-80-0) → (5-ethylcarbamate-3-morpholinyl-1,2,3-oxadiazolium-4-yl)triphenylborate

Conditions	Yield
Stage #1: molsidomine With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: triphenylborane In tetrahydrofuran at -10 - 20℃; for 4h; Inert atmosphere;	87%

molsidomine (25717-80-0) + methyl iodide (74-88-4) → 6-ethoxycarbonyl-4-methylthio-3-morpholinyl sydnone imine

Conditions	Yield
Stage #1: molsidomine With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With sulfur In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #3: methyl iodide In tetrahydrofuran at 0 - 20℃; for 2.5h; Inert atmosphere;	85%

molsidomine (25717-80-0) + mercury dichloride → bis(6-ethoxycarbonyl-3-morpholinyl-sydnone imine-4-yl)mercury(II)

Conditions	Yield
Stage #1: molsidomine With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: mercury dichloride In tetrahydrofuran at 0 - 20℃; for 3.5h; Inert atmosphere;	78%

molsidomine (25717-80-0) → ethyl-N-(1-morpholinyl-1-thioxo-ethan-2-one)carbamate

Conditions	Yield
Stage #1: molsidomine With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With sulfur In tetrahydrofuran at 0℃; for 2.5h; Inert atmosphere; Stage #3: With water In tetrahydrofuran Inert atmosphere;	63%

sulfur (10544-50-0) + (triphenylphosphine)gold(I) chloride (14243-64-2) + molsidomine (25717-80-0) → ((6-ethoxycarbonyl-3-morpholinyl-sydnone imine-4-yl)thio)(triphenylphosphine)gold(I)

Conditions	Yield
Stage #1: molsidomine With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: sulfur In tetrahydrofuran at 0℃; Inert atmosphere; Stage #3: (triphenylphosphine)gold(I) chloride In tetrahydrofuran at 0 - 20℃; for 3.5h; Inert atmosphere;	36%

molsidomine (25717-80-0) → morpholine (110-91-8)

Conditions	Yield
In methanol for 0.166667h; Product distribution; Kinetics; Irradiation; var. of solvent, also additives;

molsidomine (25717-80-0) + peracetylated β-cyclodextrin (23739-88-0) → C9H14N4O4*C84H112O56

Conditions	Yield
With carbon dioxide at 45℃; under 258776 Torr; for 0.5h;

molsidomine (25717-80-0) → trans-chloro(N3-morpholinyl-N6-ethylestersydnonimine-4-yl)bis(triphenylphosphine)palladium(II)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium hexamethyldisilazane / tetrahydrofuran-d8; tetrahydrofuran / Inert atmosphere 2: tetrahydrofuran / -50 - 20 °C / Inert atmosphere View Scheme

molsidomine (25717-80-0) → C9H13(2)HN4O4

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium hexamethyldisilazane / tetrahydrofuran-d8; tetrahydrofuran / Inert atmosphere 2: [D3]acetonitrile / 20 °C View Scheme

molsidomine (25717-80-0) → 4-(methylseleno)molsidomine

Conditions	Yield
Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran-d8; tetrahydrofuran / Inert atmosphere 2.1: selenium / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 2.2: 0 - 20 °C / Inert atmosphere View Scheme

molsidomine (25717-80-0) → (N3-morpholinyl-N6-ethoxycarbonyl-sydnonimine-4-yl)(triphenylphosphine)gold(I)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium hexamethyldisilazane / tetrahydrofuran-d8; tetrahydrofuran / Inert atmosphere 2: tetrahydrofuran / -50 - 20 °C / Inert atmosphere View Scheme

4-chlorobenzaldehyde (104-88-1) + molsidomine (25717-80-0) → 4-[(4'-chlorophenyl)hydroxymethyl]-3-morpholyl-N6-ethoxycarbonylsydnone imine

Conditions	Yield
Stage #1: molsidomine With n-butyllithium In tetrahydrofuran; hexane at -80 - 20℃; for 0.35h; Stage #2: 4-chlorobenzaldehyde In tetrahydrofuran; hexane at 20℃; for 0.333333h; Reagent/catalyst; Time;

1-methoxy-N,N-dimethylmethanaminium methylsulphate + molsidomine (25717-80-0) → 4-formyl-3-morpholino-N6-ethoxycarbonylsydnone imine

Conditions	Yield
Stage #1: molsidomine With n-butyllithium In tetrahydrofuran; hexane at -80 - 20℃; for 0.183333h; Inert atmosphere; Stage #2: 1-methoxy-N,N-dimethylmethanaminium methylsulphate In tetrahydrofuran; hexane; N,N-dimethyl-formamide at 20℃; for 0.333333h; Reagent/catalyst; Inert atmosphere;	66 %Spectr.

Upstream product

• 541-41-3 chloroformic acid ethyl ester 
• 16142-27-1 Linsidomine hydrochloride 

Downstream Products

• 110-91-8 morpholine 

Relevant articles and documents

Anionic N-heterocyclic carbenes derived from sydnone imines such as molsidomine. Trapping reactions with selenium, palladium, and gold

The sydnone imines Molsidomine and 5-(benzoylimino)-3-(2-methoxyphenyl)-1,2,3-oxadiazolium-2-ide gave anionic N-heterocyclic carbenes on deprotonation at C4 which were trapped as methylated selenium adducts, gold complexes (X-ray analysis) as well as palladium complexes (X-ray analysis). The 13C NMR resonance frequencies of the carbene carbon atom are extremely shifted upfield and appear at δ = 142.1 ppm (Molsidomine carbene) and δ = 159.8 ppm (sydnone imine carbene). The Pd complexes were applied as catalysts in Suzuki-Miyaura and Sonogashira-Hagihara cross-coupling reactions.

Spherical granules having core and their production

The spherical granules having a core coated with spraying powder containing a drug and low substituted hydroxypropylcellulose, because of their excellent hardness, can be coated further evenly, (e.g. sustained release coating, gastric coating, enteric coating), and at the time the granules are excellent in disintegration.