635705-72-5

Upstream product

• 253168-94-4 2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulfonyl)eth-2-ylamine 
• 608141-43-1 (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanamine-(S)-2-acetamido-4-methylpentanoate 
• 5434-20-8 3-aminophthalic acid 
• 608141-42-0 (S)-2-[1 (3-ethoxy-4-methoxyphenyl)]-1-methanesulfonyl-2-ethylamine 
• 6296-53-3 3-acetylaminophthalic anhydride 
• 608141-41-9 Apremilast 
• 603-11-2 3-nitrophthalic acid 
• 6946-22-1 3-aminophthalic acid hydrochloride 
• 1450657-28-9 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethan-1-one 
• 97966-31-9 3-ethoxy-4-methoxybenzoic acid methyl ester 
• 641-70-3 3-nitrophthalic acid anhydride 
• 608142-27-4 (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)-ethylamine 
• 613-70-7 2-methoxyphenyl acetate 
• 66037-04-5 1-acetoxy-5-bromo-2-methoxybenzene 

Downstream Products

• 608141-41-9 Apremilast 
• 1384814-94-1 (1S)-N-{2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-2-hydroxy-acetamide 
• 1384440-09-8 (S)-N-{2-[1-(3,4-dihydroxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-2-hydroxy-acetamide 
• 1384440-08-7 (S)-N-{2-[1-(3-ethoxy-4-hydroxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-2-hydroxy-acetamide 
• 1384439-80-8 (S)-4-Amino-2-[1-(3,4-dihydroxy-phenyl)-2-methanesulfonyl-ethyl]-isoindole-1,3-dione 
• 1384967-19-4 (1S)-2-benzyloxy-N-{2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-acetamide 

Relevant academic research and scientific papers

Methods for preparation of apremilast

The present invention discloses a method for preparation of Apremilast. β-phthalimino vinylsulfones are reacted through the asymmetric addition reaction to form an addition product, and the drug of Apremilast can be obtained from the addition product through simple reactions. The method is a process for synthesizing Apremilast in a more efficient way.

Chain hydrocarbon substituted isoindoline -1, 3 - diketone PDE4 inhibitor and medicinal use thereof

The invention relates to a compound shown I and a racemate thereof. A stereoisomer, a tautomer, an isotope label, a solvate, a polymorph, an ester, a prodrug or a pharmaceutically acceptable salt thereof, and a preparation method thereof, and a medical use thereof, the structure of said formula I being as follows.

Asymmetric Synthesis of β-Aryl β-Imido Sulfones Using Rhodium Catalysts with Chiral Diene Ligands: Synthesis of Apremilast

A chiral rhodium(I)-diene catalyst enabled the one-step synthesis of β-aryl β-imido sulfones under mild reaction conditions. By selection of the chiral diene ligand L1a or L2, each enantiomer of the chiral β-aryl β-imido sulfone target can be accessed with high stereoselectivity. Demonstration of the scope of the reaction, which includes the synthesis of an N-protected chiral β-amino β-phenyl sulfone, culminated with the efficient synthesis of the heteroatom-rich active pharmaceutical ingredient apremilast.

PROCESS FOR PREPARATION OF APREMILAST

The present invention relates to a process for preparation of apremilast. The present invention relates to p-xylene solvate of apremilast and process for its preparation.

Synthesis and refining method of apremilast

The invention relates to the field of chemical synthesis, in particular to a novel method for synthesizing and refining apremilast. A new starting raw material is introduced; in a preparation process, by selection of the type and the proportion of a specific solvent and control over reaction conditions, the product yield is high, and particle size of a refined product is qualified; no secondary smashing treatment is needed, and the optical purity is improved; therefore, the requirement on experimental equipment and the cost are reduced, the toxicity is reduced, and occurrence of adverse events is avoided.

IMPROVED PROCESS FOR THE PREPARATION OF APREMILAST

The present invention relates to novel processes for the preparation of apremilast of formula I, or a pharmaceutically acceptable salt thereof.

A synthetic apps is special method for the preparation of intermediates

The invention relates to a preparation method for synthesizing an apremilast intermediate. The preparation method comprises the following steps of: carrying out condensation reaction on 3-ethoxyl-4-methoxyl-benzoate and dimethyl sulfone under an alkaline condition to generate 2-(3-ethoxy-4-methoxyphenyl)-1-methylsulfonyl acetone; reacting the compound II and chiral amine in the presence of an acidic catalyst to obtain 1-N-substituted amino-1-(3-ethoxyl-4-methoxyl) phenyl-2-methylsulfonyl ethylene (III), and directly hydrogenating the obtained compound III in the presence of a hydrogenation catalyst without separating the compound III to obtain a product (S)-1-(3-ethoxyl-4-methoxyl) phenyl-2-methanesulfonyl ethylamine (I), namely the apremilast intermediate, wherein the apremilast intermediate can be further prepared into N-acetyl L-leucinate. The invention also provides a preparation method of apremilast. The preparation method disclosed by the invention has the advantages of simple process flow, safety, environmental friendliness and low cost and is favorable to clean industrialized production.