ChemicalBook CAS DataBase List Apremilast

Apremilast synthesis

3synthesis methods

Product Name:Apremilast
CAS Number:608141-41-9
Molecular formula:C22H24N2O7S
Molecular Weight:460.5

Apremilast, also known as CC-10004, is a thalidomide analog and is an orally available small molecule inhibitor of phosphodiesterase 4 (PDE4). Apremilast specifically inhibits PDE4 and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It has anti-inflammatory activity. Apremilast was approved by the USFDA in March 2014 for treatment of adults with active psoriatic arthritis. It is also being tested for its efficacy in treating other chronic inflammatory diseases such as ankylosing spondylitis, Behcet's disease, and rheumatoid arthritis.

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

ROUTE 4

ROUTE 5

ROUTE 6

Syu, Jin-Fong; Gopula, Balraj; Jian, Jia-Hong; Li, Wei-Sian; Kuo, Ting-Shen; Wu, Ping-Yu; Henschke, Julian P.; Hsieh, Meng-Chi; Tsai, Ming-Kang; Wu, Hsyueh-Liang. Asymmetric Synthesis of β-Aryl β-Imido Sulfones Using Rhodium Catalysts with Chiral Diene Ligands: Synthesis of Apremilast. Organic Letters. Volume 21. Issue 12. Pages 4614-4618. Journal; Online Computer File. (2019).

6296-53-3 Synthesis

6296-53-3
304 suppliers
$6.00/250mg

608141-42-0 Synthesis

(S)-1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl)ethanaMine

608141-42-0
224 suppliers
$10.00/250mg

608141-41-9
496 suppliers
$50.00/1g

Yield:608141-41-9 97%

Reaction Conditions:

with acetic acid for 1 h;Reflux;Large scale;

Steps:

3 Preparation of apremilast

The unbaked product (728 g after drying), glacial acetic acid (4. 2 L), (S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethanamine(1570 g, 99.3%) Followed by adding the reaction flask, heating to reflux reaction for 1 hour, After the TLC was detected, the reaction was stopped and the reaction was terminated. The reaction was terminated under reduced pressure, and 10L of methylene chloride was dissolved. After washing with 5 L of water, 5 L of water saturated with aqueous sodium bicarbonate, 5 L of saturated sodium chloride, dried over anhydrous magnesium sulfate, Concentrated to dry, add anhydrous ethanol 10L, reflux 30 minutes, filtration, ethanol washing, 60 ° C drying to obtain product 1584g, the yield of 97%, HPLC 99. 8% or more, 99.2%.

References:

CN105294534,2016,A Location in patent:Paragraph 0030; 0031

6296-53-3 Synthesis

6296-53-3
304 suppliers
$6.00/250mg

608141-43-1 Synthesis