Preparation methods of losartan potassium and preparation thereof

A technology of losartan potassium and losartan, applied in the field of chemical pharmacy, can solve problems such as high production cost and complicated subsequent procedures, and achieve the effect of high yield

CN102276586BActive Publication Date: 2014-04-09YANGTZE RIVER PHARM GRP SICHUAN HAIRONG PHARM CO LTD +2
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Publication Date
2014-04-09

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Abstract

The invention discloses preparation methods of losartan potassium and a preparation thereof. The losartan potassium is prepared by the steps of: by taking 2-butyl-5(4)-formoxyl-4(5)-trichlorophenidin (II) and N-(triphenylmethyl)-5-[(4'-brooethyl)-xenyl-2-]tetrazole (III) as raw materials and adopting tetrabutyl ammonium bromide as a phase-transfer catalyst for N-alkylating, performing condensation, reduction and deprotection to synthesize losartan; and salifying the obtained losartan with potassium hydroxide to synthesize raw material losartan potassium. The raw material losartan potassium is mixed with proper auxiliaries to prepare a medicinal preparation. The preparation methods in the invention have the characteristics of mild requirements on production conditions, simplicity in operation and high yield, and are suitable for industrial production.
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Description

technical field

[0001] The invention relates to the field of chemical pharmacy. Especially the synthesis process of losartan potassium, sartan potassium hydrate, new crystal form IV losartan potassium and its solvate, new crystal form V losartan potassium and its solvate; the preparation of the compound Methods; compositions containing said compounds and uses of said compounds in medicine. Background technique

[0002] In 1995, losartan potassium became the first non-peptide AT antagonist approved by the US Food and Drug Administration for clinical use. In particular, Falsartan is approved for the treatment of high blood pressure alone or in combination with other antihypertensive drugs. Falsartan can be administered orally as its potassium salt. Fusartan potassium tablets (Coz, aar.: Merck) containing the only active ingredient and compound fusartan potassium tablets (Hyzaar.: Merck) containing hydrogen acetaminophen are available by prescription.

[0003] Falsartan pot...

Examples

Embodiment Construction

[0012] Below, in conjunction with embodiment the content of the present invention is described in detail.

[0013] 1, the preparation of raw material losartan potassium

[0014] Detailed steps

[0015] ①2-Butyl-4-chloro-5-(hydroxymethyl)-1-[[2'-[(triphenylmethyl)-tetrazolium-5-]biphenyl-4-]methyl] Imidazole (trityl losartan)

[0016] Main feeding ratio:

[0017] 2-Butyl-5(4)-formyl 186.5g (FW: 186.5) 1.0mol-4(5)-chloroimidazole(II)

[0018] N-(triphenylmethyl)-5-[(4'-557.0g (FW:557) 1.0mol bromomethyl)-biphenyl-2-]tetraazol

[0019] Azole(III)

[0020] Tetrabutylammonium bromide 32.2g (FW: 322) 0.1mol

[0021] Sodium hydroxide 80.0g (FW: 40) 2.0mol

[0022] Sodium borohydride 38.0g (FW: 38) 1.0mol

[0023] 2-Butyl-5(4)-formyl-4(5)-chloroimidazole (II) 186.5g (1.0mol), tetrabutylammonium bromide 32.2g (0.1mol), 1.0mol / L hydroxide Mix 2000ml (2.0mol) of sodium with 2.0L of dichloromethane, and add N-(triphenylmethyl)-5-[(4'-bromomethyl)-biphenyl-2-]tetrazolium ( III) ...