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Preparation method of S-type apremilast

A compound and reaction temperature technology, applied in organic chemistry and other fields, can solve the problems of large environmental pollution and high production cost

Inactive Publication Date: 2015-04-01
NANJING CORE TECH CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] The metal catalyst bis(1,5-cyclooctadiene)-rhodium trifluoromethanesulfonate (I) and (R)-(-)-1-[(S)-2-bis Phenylphosphinoferrocenylethyldi-tert-butylphosphorus, which has great environmental pollution and high production cost

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  • Preparation method of S-type apremilast
  • Preparation method of S-type apremilast
  • Preparation method of S-type apremilast

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Embodiment Construction

[0028] The above-mentioned content of the present invention will be described in further detail below through the embodiment form, but this should not be interpreted as the scope of the above-mentioned theme of the present invention is limited to the following embodiments, all technologies realized based on the above-mentioned content of the present invention belong to this invention the scope of the invention.

[0029] The preparation of embodiment S type apremilast

[0030] (1) Synthesis of compound 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine L-leucine salt (formula (Ⅲ))

[0031] In a 1000mL four-neck round bottom flask, install mechanical stirring, reflux condenser, and thermometer, add 500ml of methanol to the round bottom flask, start stirring, add 64g of 1-(3-ethoxy-4-methoxyphenyl) -2-(methylsulfonyl)ethylamine, heat up to 70~80℃, heat to reflux to 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine Dissolve completely, add 22g of N-acetyl-L-leucin...

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Abstract

The invention discloses a preparation method of apremilast (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-mesylethyl]-4-acetamidoisoindolinyl-1,3-dione. The method comprises the following steps: (1) converting a compound 1-(3-ethoxy-4-methoxyphenyl)-2-(methanesulfonyl)ethylamine racemate disclosed as Formula (II) into a salification substance disclosed as Formula (III) by using a resolving agent; and (2) connecting the compound disclosed as Formula (III) with 3-acetamidophthalic anhydride to obtain the compound disclosed as Formula (I). The method can be utilized to obtain the stable apremilast acceptable finished product, has the advantages of mild technological conditions, simple after-treatment, high purity and low reaction cost, and can easily implement industrial production.

Description

technical field [0001] The invention belongs to the technical field of chemical drug synthesis, and relates to S-type apremilast (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4 - Process for the preparation of acetamidoisoindoline-1,3-dione. Background technique [0002] Apremilast (apremilast), the chemical name is (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetamidoiso Indoline-1,3-dione compound, the structural formula is as follows: [0003] [0004] Apremilast (trade name Otezla), independently developed by Xinji Pharmaceuticals, is an oral small molecule phosphodiesterase 4 (PDE4) inhibitor for the treatment of psoriatic arthritis and plaque psoriasis sick. Apremilast selectively inhibits PDE4, prevents rheumatoid synoviocytes from secreting tumor necrosis factor α (TNF-α) and produces anti-inflammatory activity, which can reduce joint swelling and improve the physiological functions of joints. [0005] There are many synthetic met...

Claims

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Application Information

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IPC IPC(8): C07D209/48
CPCC07D209/48
Inventor 王雪根何凌云李晓静郭莉芹
Owner NANJING CORE TECH CO LTD
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