Preparation method of paricalcitol

A technology for paricalcitol and compounds, which is applied in the field of preparation of paricalcitol, can solve the problems of unenvironmental protection, low yield of Julia coupling olefination, poor selectivity, etc., and achieves convenient operation and reagents. Simple, short route effect

Inactive Publication Date: 2013-07-10
CHONGQING TAIHAO PHARM CO LTD
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0009] The second route is longer (WO2008053961, JP053392300), with more than seventeen steps
Among them, the Julia coupling olefination yield used when connecting the side chain is low, and the use of Na-Hg is not environmentally friendly; the several-step reaction used when converting the extracyclic double bond is not very good, such as dihydroxy The oxidation reaction may oxidize the double bond of the side chain, etc.

Method used

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  • Preparation method of paricalcitol
  • Preparation method of paricalcitol

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Embodiment Construction

[0036] For further elaborating the technical means and effects that the present invention takes to reach the intended invention purpose, below in conjunction with accompanying drawing and preferred embodiment, to its specific implementation, method, Steps, features and effects thereof are described in detail below.

[0037] The method of the present invention uses vitamin D2 as a starting material, after protecting the three-membered ring, protecting the hydroxyl group to obtain compound 7,

[0038]

[0039] R 1 Can be acetyl, benzoyl, t-butyldimethylsilyl, triethylsilyl, methoxymethyl. Compound 7 was cut off the double bonds on the outer ring and the side chain by one ozonation reaction, and compound 8 was obtained by reduction, and compound 9 was obtained by selective esterification.

[0040]

[0041] R 2 Can be acetyl, benzoyl.

[0042] Compound 9 was ring-opened to obtain compound 10, and the hydroxyl group was selectively protected to obtain compound 11.

[004...

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Abstract

The invention relates to a preparation method of paricalcitol, which is characterized in that after hydroxyl in the vitamin D2 is protected by p-toluenesulfonates, in the presence of alkali, intramolecular cyclization reaction happens in methanol to generate a compound 5; the compound 5 undergoes allylic oxidation and hydroxyl is protected to obtain a key intermediate 7; in the presence of ozone,the side chains and exocyclic terminal double bonds of the key intermediate 7 are cut off to obtain a compound 8; the primary hydroxyl in the compound 8 is selectively protected, a three-membered ring is opened in the presence of acid and then hydroxyl is protected to obtain a key intermediate 11; after the secondary hydroxyl in the key intermediate 11 is protected by sulphonate, a compound 12 isobtained through reduction by LiAlH4; a compound 13 is obtained after the compound 12 is subjected to Swern oxidation and carries out Wittig reaction with the compound 12 to obtain a compound 14; andthe target compound can be obtained by removing the protective group in the compound 14. The reagents used in the method are simple and are convenient to operate, the reactions concerning regioselectivity and stereoselectivity are few, the route is shorter and 12 steps of reactions are carried out.

Description

technical field [0001] The present invention relates to the synthesis of a compound, in particular to a preparation method of paricalcitol. Background technique [0002] Paricalcitol (active vitamin D treatment drug, Paricalcitol) is a drug for the prevention and treatment of secondary hyperparathyroidism (SHPT), which is effective for stage III and IV chronic kidney disease before dialysis and transplantation. SHPT in patients with CKD has shown preventive and therapeutic effects, and has become the most widely used drug for the prevention and treatment of SHPT in patients with dialysis. Serum phosphorus levels had minimal impact, and PTH reduction was a key indicator of efficacy of SHPT treatment. The binding of paricalcitol [0003] [0004] See formula 1 for construction: 1 Paricalcitol formula 1 [0005] Synthetic Paricalcitol mainly contains the following two methods in the prior art: [0006] The first route (US5281731, US5086191) adopts the strategy of converg...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C401/00
CPCY02P20/55
Inventor 李瀛薛吉军张宪恕徐少军
Owner CHONGQING TAIHAO PHARM CO LTD
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