Dimethyl Fumarate

Base Information

• Chemical Name: Dimethyl Fumarate
• CAS No.: 624-49-7
• Deprecated CAS: 1017900-75-2
• Molecular Formula: C6H8O4
• Molecular Weight: 144.127
• Hs Code.: 29171990
• European Community (EC) Number: 210-849-0
• ICSC Number: 1732
• NSC Number: 760139,167432,25942
• UNII: FO2303MNI2
• DSSTox Substance ID: DTXSID4060787
• Nikkaji Number: J45.019G,J502.486B
• Wikipedia: Dimethyl_fumarate
• Wikidata: Q418123
• NCI Thesaurus Code: C63670
• RXCUI: 1373478
• Pharos Ligand ID: 2NLTKZFDH13N
• Metabolomics Workbench ID: 151994
• ChEMBL ID: CHEMBL2107333
• Mol file: 624-49-7.mol

Synonyms:00012, BG;12 compound, BG;2-butenedioic acid, (2E)-, dimethyl ester;201, FAG;BG 00012;BG 12 compound;BG-00012;BG-12 compound;BG00012;BG12 compound;compound, BG 12;compound, BG12;dimethyl fumarate;dimethylfumarate;FAG 201;FAG-201;FAG201;Fumaderm;Fumarate, Dimethyl;Tecfidera

Chemical Property of Dimethyl Fumarate

Chemical Property:

• Appearance/Colour: fine white crystalline powder
• Vapor Pressure: 0.475mmHg at 25°C
• Melting Point: 102-106 °C(lit.)
• Refractive Index: 1.435
• Boiling Point: 193 °C at 760 mmHg
• Flash Point: 91.1 °C
• PSA: 52.60000
• Density: 1.124 g/cm³
• LogP: -0.11140
• Storage Temp.: Store at RT.
• Solubility.: 1.6g/l
• Water Solubility.: Soluble in water (1.6 mg/ml at 20°C), methanol (30-36 mg/ml), ethanol (10 mg/ml at 25°C), DMSO (29 mg/ml at 25°C), and DMF (~12 mg/ml).
• XLogP3: 0.7
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 144.04225873
• Heavy Atom Count: 10
• Complexity: 141

Purity/Quality:

99%Min ^*data from raw suppliers

Dimethyl Fumarate ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn:Harmful
• Statements: R21:; R36/37/38:
• Safety Statements: S36/37/39:

MSDS Files:

SDS file from LookChem

Useful:

• Chemical Classes: Other Classes -> Esters, Other
• Drug Classes: Multiple Sclerosis Agents
• Canonical SMILES: COC(=O)C=CC(=O)OC
• Isomeric SMILES: COC(=O)/C=C/C(=O)OC
• Recent ClinicalTrials: Study to Evaluate the Efficacy and Safety of Dimethyl Fumarate (Tecfidera) and Peginterferon Beta-1a (Plegridy) for the Treatment of Relapsing-Remitting Multiple Sclerosis in Pediatric Participants
• Recent EU Clinical Trials: An Open-Label, Rater-Blind, Randomized, Multi-Center, Parallel-Arm, Active-Comparator Study to Assess the Efficacy and Tolerability of Ofatumumab 20mg SC monthly vs. First Line DMT-physician’s choice in the treatment of newly diagnosed RMS
• Inhalation Risk: A harmful contamination of the air will not or will only very slowly be reached on evaporation of this substance at 20 °C; on spraying or dispersing, however, much faster.
• Effects of Short Term Exposure: The substance is irritating to the skin and respiratory tract. The substance is severely irritating to the eyes.
• Effects of Long Term Exposure: Repeated or prolonged contact with skin may cause dermatitis.
• Description: In March 2013, the US FDA approved dimethyl fumarate for the treatment of relapsing forms of multiple sclerosis (MS). Dimethyl fumarate is the newest oral therapeutic for MS. While its mechanism is not completely understood, dimethyl fumarate increases anti-inflammatory cytokines (IL-10, IL-4, and IL-6), decreases proinflammatory cytokines (IL-1β, IL-6, and TNF-α), and activates the Nrf2 pathway to protect neuronal cells. Nrf2 is activated by covalent bond-forming electrophiles such as dimethyl fumarate, a Michael acceptor. Dimethyl fumarate has been used for the treatment of psoriasis in Europe since 1994 and has a favorable long-term safety profile. An exploratory study in patients with relapsing remitting MS showed significant reductions in MS lesions after 18 weeks of treatment with 720 mg/day of dimethyl fumarate. Evaluation of dimethyl fumarate in a mouse experimental autoimmune encephalomyelitis model of MS resulted in reduced spinal cord macrophage inflammation. Dimethyl fumarate is obtained in high purity by esterification of fumaric acid with methanol and catalytic sulfuric acid.
• Uses: Dimethyl fumarate acts as an immunomodulator. It is also used in cycloaddition reactions involving ylides, benzenes and amino acids. It is added to food grains,tobacco,leather and preservation. Clothing
• Clinical Use: Treatment of relapsing-remitting multiple sclerosisTreatment of moderate to severe plaque psoriasis
• Drug interactions: Potentially hazardous interactions with other drugsAminophylline and theophylline: enhanced effect of aminophylline and theophylline.Anaesthetics: enhanced hypotensive effect. Anti-arrhythmics: increased risk of bradycardia, AV block and myocardial depression with amiodarone; increased risk of bradycardia and myocardial depression with dronedarone.Antibacterials: metabolism increased by rifampicin; metabolism possibly inhibited by clarithromycin, erythromycin and telithromycin.Antidepressants: enhanced hypotensive effect with MAOIs; concentration of imipramine and possibly other trycyclics increasedAntiepileptics: effect probably reduced by barbiturates, fosphenytoin, phenytoin, and primidone; enhanced effect of carbamazepine; increased levels of fosphenytoin and phenytoin.Antifungals: negative inotropic effect possibly increased with itraconazole.Antihypertensives: enhanced hypotensive effect; increased risk of first dose hypotensive effect of postsynaptic alpha-blockersAntipsychotics: concentration of lurasidone increased.Antivirals: concentration increased by atazanavir and ritonavir - reduce dose of diltiazem with atazanavir; concentration reduced by efavirenz; use telaprevir with caution.Avanafil: possibly increases avanafil concentration.Beta-blockers: risk of bradycardia and AV block if co-prescribed with beta-blockers.Cardiac glycosides: increased digoxin concentration.Ciclosporin: increased ciclosporin concentrations.Cilostazol: increased cilostazol concentration - avoid.Colchicine: possibly increased risk of colchicine toxicity - suspend or reduce colchicine, avoid concomitant use in renal or hepatic failure.Cytotoxics: concentration of bosutinib, ibrutinib and olaparib possibly increased - avoid or reduce dose; possibly increased risk of bradycardia with crizotinib.Fingolimod: increased risk of bradycardia.Ivabradine: concentration of ivabradine increased - avoid.Lipid lowering drugs: concentration of lomitapide possibly increased - avoid.Sirolimus: sirolimus concentration increased.

Technology Process of Dimethyl Fumarate

There total 159 articles about Dimethyl Fumarate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 86.0%

methyl diazoacetate (6832-16-2) + 3-morpholino-but-2-enoic acid methyl ester (55261-56-8) → dimethyl cis-but-2-ene-1,4-dioate (624-48-6) + dimethylfumarate (624-49-7) + (1R,2R)-3-Methyl-3-morpholin-4-yl-cyclopropane-1,2-dicarboxylic acid dimethyl ester

Guidance literature:

copper acetylacetonate; In ethyl acetate; Heating;

DOI:10.1002/prac.19983400405

Reference yield: 84.0%

4-(pyrrolidin-1-yl)pent-3-en-2-one (23652-59-7) + methyl diazoacetate (6832-16-2) → methyl 2-acetyl-4-oxovalerate (85392-47-8) + dimethyl cis-but-2-ene-1,4-dioate (624-48-6) + dimethylfumarate (624-49-7)

Guidance literature:

copper(I) triflate; In dichloromethane; at 20 ℃; for 24h;

DOI:10.1002/prac.19983400405

Reference yield: 84.0%

methyl diazoacetate (6832-16-2) + E-methyl β-morpholino-cinnamate (137201-66-2) → dimethyl cis-but-2-ene-1,4-dioate (624-48-6) + dimethylfumarate (624-49-7) + (1R,2R)-3-Morpholin-4-yl-3-phenyl-cyclopropane-1,2-dicarboxylic acid dimethyl ester

Guidance literature:

copper acetylacetonate; In ethyl acetate; Heating;

DOI:10.1002/prac.19983400405

upstream raw materials:

methyl diazoacetate

dimethyl 2-diazosuccinate

dimethyl 2-bromosuccinate

diethyl ether

Downstream raw materials:

dimethyl 3-phenyl-4,5-dihydroisoxazole-4,5-dicarboxylate

dimethyl (exo,endo)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate

dimethyl bicyclo<2,2,2>oct-5-ene-endo-2,exo-3-dicarboxylate

dimethyl trans-cyclohex-4-ene-1,2-dicarboxylate

Refernces

• 1、 Hiraki, Katsuma,Itoh, Toshihiro,Eguchi, Katsuya,Onishi, Masayoshi. "REACTIONS OF BENZYLCHLOROBIS(TRIPHENYLPHOSPHINE)PALLADIUM(II) WITH DIMETHYL ACETYLENEDICARBOXYLATE". . p. C16 - C20. Retrieved 1983.
• 2、 Cook,Voges, Andrea B,Kammrath, Aster E. "Aminal-catalyzed isomerization of and addition to dimethyl maleate". . p. 7349 - 7352. Retrieved 2001.
• 3、 Komatsu, Mitsuo,Okada, Hirofumi,Akaki, Tatsuo,Oderaotoshi, Yoji,Minakata, Satoshi. "Generation and cycloaddition of polymer-supported azomethine ylide via a 1,2-silatropic shift of α-silylimines: Traceless synthesis of pyrrolidine derivatives". . p. 3505 - 3508. Retrieved 2002.
• 4、 Lam, Ying-Pong,Lam, Zachary,Yeung, Ying-Yeung. "Zwitterion-Catalyzed Isomerization of Maleic to Fumaric Acid Diesters". . p. 1183 - 1190. Retrieved 2021/01/09.
• 5、 Chen, Kun-Quan,Shen, Jie,Wang, Zhi-Xiang,Chen, Xiang-Yu. "A donor-acceptor complex enables the synthesis of: E -olefins from alcohols, amines and carboxylic acids". . p. 6684 - 6690. Retrieved 2021/05/31.