Tofisopam

Base Information

• Chemical Name: Tofisopam
• CAS No.: 22345-47-7
• Molecular Formula: C₂₂H₂₆N₂O₄
• Molecular Weight: 382.459
• European Community (EC) Number: 244-922-3
• UNII: UZC80HAU42
• DSSTox Substance ID: DTXSID3023681
• Nikkaji Number: J11.504E
• Wikipedia: Tofisopam
• Wikidata: Q945537
• NCI Thesaurus Code: C90791
• Pharos Ligand ID: KZFLKDCNGXJS
• Metabolomics Workbench ID: 43726
• ChEMBL ID: CHEMBL404216
• Mol file: 22345-47-7.mol

Synonyms:1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine;dextofisopam;EGYT-341;Grandaxin;levotofisopam;tofisopam;tofizopam

Chemical Property of Tofisopam

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 7.13E-09mmHg at 25°C
• Melting Point: 155-159°C
• Refractive Index: 1.558
• Boiling Point: 478.973 °C at 760 mmHg
• PKA: 7.29±0.40(Predicted)
• Flash Point: 195.179 °C
• PSA: 61.64000
• Density: 1.155 g/cm³
• LogP: 3.31270
• Solubility.: DMSO: ~14 mg/mL
• XLogP3: 3.2
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 6
• Exact Mass: 382.18925731
• Heavy Atom Count: 28
• Complexity: 579

Purity/Quality:

99.9% ^*data from raw suppliers

Tofisopam ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,N
• Hazard Codes: Xn,N
• Statements: 22-50
• Safety Statements: 60-61

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CCC1C(=NN=C(C2=CC(=C(C=C12)OC)OC)C3=CC(=C(C=C3)OC)OC)C
• Therapeutic Function: Tranquilizer

Technology Process of Tofisopam

There total 20 articles about Tofisopam 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: 97.0%

(-)-Tofisopam (82059-51-6) → tofisopam (22345-47-7,914303-48-3,914303-49-4,914303-50-7,914303-51-8)

Guidance literature:

With potassium tert-butylate; In tetrahydrofuran; at 0 - 20 ℃; for 2h; Product distribution / selectivity;

Reference yield: 73.0%

{4,5-dimethoxy-2-[1-(2-methyl-[1,3]dioxolan-2-yl)propyl]phenyl}(3,4-dimethoxyphenyl)methanone + hydrazine hydrate (7803-57-8,79785-97-0) → tofisopam (22345-47-7,914303-48-3,914303-49-4,914303-50-7,914303-51-8)

Guidance literature:

{4,5-dimethoxy-2-[1-(2-methyl-[1,3]dioxolan-2-yl)propyl]phenyl}(3,4-dimethoxyphenyl)methanone; With hydrogenchloride; acetic acid; In water; at 20 ℃; for 1h;

In methanol; water; for 0.5h; Reflux;

hydrazine hydrate; In methanol; water; at 20 ℃; for 1.5h;

DOI:10.3987/COM-13-S(S)15

Reference yield: 60.0%

3-[2-(3,4-dimethoxybenzoyl)-4,5-dimethoxyphenyl]pentan-2-one (15462-91-6) → tofisopam (22345-47-7,914303-48-3,914303-49-4,914303-50-7,914303-51-8)

Guidance literature:

With hydrazine hydrate; In ethanol; for 1h; Heating;

upstream raw materials:

3-[2-(3,4-dimethoxybenzoyl)-4,5-dimethoxyphenyl]pentan-2-one

1-(3,4-dimethoxyphenyl)-6,7-dimethoxy-4-ethyl-3-methylisochroman

3,4-dimethoxy-benzaldehyde

3-(3,4-dimethoxyphenyl)-2-pentanol

Downstream raw materials:

1-(3,4-dimethoxyphenyl)-7,8-dimethoxy-3,4-dimethyl-5-ethyl-5H-2,3-benzodiazepin-3-ium iodide

4-ethyl-3-methyl-6,7-dimethoxy-1-(3,4-dimethoxyphenyl)isoquinoline

1-(3,4-dimethoxyphenyl)-7,8-dimethoxy-5-ethyl-4-methyl-5H-2,3-benzodiazepine hydrochloride

(+)-Tofisopam

Refernces

New, lithiation-based synthesis of tofisopam, A 2,3-benzodiazepine type anxiolytic drug

10.3987/COM-13-S(S)15

The study presents a new, environmentally friendly synthesis method for tofisopam, a 2,3-benzodiazepine type anxiolytic drug, which avoids the use of toxic chromium(VI) oxide reagents traditionally used in its production. The research focuses on replacing the hazardous chromium-based oxidation step with a lithiation-based approach to produce the key intermediate, a keto-ketal compound. The chemicals used in the study include (3,4-dimethoxyphenyl)acetone, bromine, lithium compounds (hexyllithium), 3,4-dimethoxybenzoyl chloride, and hydrazine, among others. These chemicals serve various purposes in the synthesis process, such as starting materials, reagents for protection and deprotection of functional groups, and agents for the lithiation and cyclization steps, ultimately leading to the formation of tofisopam without the environmental and health risks associated with chromium salts.