608141-44-2

Basic information

• Product Name: (R)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide
• Synonyms: (R)-Apremilast
• CAS NO: 608141-44-2
• Molecular Formula: C₂₂H₂₄N₂O₇S
• Molecular Weight: 460.50016
• EINECS: -0
• Mol File: 608141-44-2.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 741.3±60.0 °C(Predicted)
• Appearance: /
• Density: 1.381±0.06 g/cm3(Predicted)
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 14.01±0.20(Predicted)
• CAS DataBase Reference: (R)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide(608141-44-2)
• EPA Substance Registry System: (R)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide(608141-44-2)

Safety Data

• Hazardous Substances Data: 608141-44-2(Hazardous Substances Data)

Usage

Description

(R)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide, also known as (R)-Apremilast, is an enantiomer of Apremilast (A729700). It is an oral phosphodiesterase 4 (PDE4) inhibitor with potential applications in the treatment of various inflammatory and autoimmune diseases.

Uses

Used in Pharmaceutical Industry:
(R)-Apremilast is used as a therapeutic agent for the treatment of psoriatic arthritis. It works by inhibiting the activity of phosphodiesterase 4, an enzyme involved in the regulation of inflammatory processes. This inhibition leads to a decrease in the production of inflammatory mediators, thereby alleviating the symptoms of psoriatic arthritis.
Additionally, due to its PDE4 inhibitory properties, (R)-Apremilast may have potential applications in the treatment of other inflammatory and autoimmune diseases, although further research is needed to explore these possibilities.

Upstream product

• 6296-53-3 3-acetylaminophthalic anhydride 
• 608142-27-4 (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)-ethylamine 
• 6118-65-6 3-acetamidophthalimide 
• 1450657-24-5 (R)-3-ethoxy-4-methoxy-α-[(methylsulfonyl)methyl]benzyl alcohol 
• 31526-71-3 3-ethoxy-4-methoxy-acetophenone 
• 1450657-28-9 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethan-1-one 
• 613-70-7 2-methoxyphenyl acetate 
• 66037-04-5 1-acetoxy-5-bromo-2-methoxybenzene 
• 37942-01-1 5-bromo-2-methoxyphenol 
• 52849-52-2 1-Bromo-3-ethoxy-4-methoxybenzene 
• 915201-13-7 (3-ethoxy-4-methoxyphenyl)boronic acid 
• 2518-24-3 3-aminophthalimide 
• 90-05-1 2-methoxy-phenol 
• 253168-94-4 2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulfonyl)eth-2-ylamine 

Relevant articles and documents

Chemoenzymatic synthesis of apremilast: A study using ketoreductases and lipases

The key step in the chemoenzymatic synthesis of apremilast was to produce the chiral alcohol (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanol, (R)-3. Two enzymatic approaches were evaluated to obtain (R)-3, one using ketoreductases and the other lipases. Bioreduction of 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanone (2), using ketoreductase KRED.P2-D12, led to (R)-3 with 48% conversion and 93% enantiomeric excess (ee). Kinetic resolution of rac-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl acetate (rac-4), via hydrolysis reaction, with 20% of n-butanol, catalyzed by lipase from Aspergillus niger yielded (R)-3 with > 99% ee, 50% conversion and E-value (enantiomeric ratio) > 200. The reaction between enantiomerically pure (R)-3 and 4-acetylamino-isoindol-1,3-dione (8) afforded apremilast in 65% yield and 67% ee.

Synthesis of Substituted β-Functionalised Styrenes by Microwave-Assisted Olefin Cross-Metathesis and Scalable Synthesis of Apremilast

Preparation of diversely substituted β-functionalised styrenes by microwave-assisted olefin cross-metathesis (CM) is described. This method can be also employed in the synthesis of β-deuterated α,β-unsaturated sulfones from inexpensive allylbenzenes, though unprecedented one-pot isomerisation/deuteration/cross-metathesis sequence. One of such obtained CM products has been utilised in a new scalable synthesis of Apremilast (6), a potent and orally active phosphodiesterase 4 and tumour necrosis factor-α inhibitor. The same strategy was used in synthesis of an optical antipode of 6, ent-Apremilast.

A SYNTHETIC PATHWAY TOWARDS APREMILAST

The present invention relates to an asymmetric process for providing N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide (apremilast) or a pharmaceutically acceptable salt or solvate thereof.