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Method for preparing talipexole

An allyl and amino technology, which is applied in the field of preparation of talixol, can solve the problems of high cost, long steps, and difficulty in industrialization, and achieve the effects of low production cost, short reaction steps, and no three wastes

Active Publication Date: 2010-03-10
SHANGHAI HAOYUAN MEDCHEMEXPRESS CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In view of this, the present invention provides a new preparation method in order to solve the shortcomings of existing talixol preparation techniques, such as long steps, high cost, and difficult industrialization. The method has the advantages of simple process, cheap and easy-to-obtain raw materials, high yield and high safety, and is suitable for industrial production

Method used

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  • Method for preparing talipexole

Examples

Experimental program
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Effect test

Embodiment 1

[0029] (1) Preparation of ethyl 3-allylaminopropionate

[0030] 100g (0.1mol) ethyl acrylate, 57g allylamine, dissolved in 500ml ethanol, reacted at 30°C for 2 hours, spin off the solvent, and distill under reduced pressure to obtain 130g of ethyl 3-allylaminopropionate with a yield of 84.2% .

[0031] 1 H NMR (300MHz, CDCl3) δ: 5.93-5.79 (m, 1H), 5.19-5.04 (m, 2H), 4.12 (q, J = 6.0 Hz, 1H), 3.25-3.22 (m, 2H), 2.85 ( t, J=6.3Hz, 2H), 2.49(t, J=6.3Hz, 2H), 1.22(t, J=6.0Hz, 3H)

[0032] (2) Preparation of ethyl 4-(allyl(3-ethoxy-3-oxopropyl)amino)butyrate

[0033] 79g (0.5mol) ethyl 3-allylaminopropionate was dissolved in 300ml acetone, 138g (1mol) potassium carbonate was added, 115g ethyl 4-bromobutyrate was added at room temperature, and reacted at 40°C for 3 hours. Pour 3 liters of ice water, stir for 20 minutes, then add 2 liters of methyl tert-butyl ether for 3 extractions, wash with saturated brine, dry, and spin-dry to obtain 140 g, and distill under reduced pressure to obtain ...

Embodiment 2

[0044] (1) Preparation of ethyl 3-allylaminopropionate

[0045] 100g (0.1mol) ethyl acrylate, 57g allylamine, dissolved in 500ml ethanol, reacted at 60°C for 2 hours, spin-dried the solvent, and distilled under reduced pressure to obtain 140g ethyl 3-allylaminopropionate with a yield of 89.2% .

[0046] (2) Preparation of ethyl 4-(allyl(3-ethoxy-3-oxopropyl)amino)butyrate

[0047] 79g (0.5mol) ethyl 3-allylaminopropionate was dissolved in 300ml DMF, 138g (1mol) potassium carbonate was added, 115g ethyl 4-bromobutyrate was added at room temperature, and reacted at 80°C for 3 hours. Pour 3 liters of ice water, stir for 20 minutes, add 2 liters of methyl tert-butyl ether for 3 extractions, wash with saturated brine, dry, and spin-dry to obtain 140 g, and distill under reduced pressure to obtain 110 g, with a yield of 81.2%.

[0048] (3) Preparation of 1-allylazacycloheptan-4-one

[0049] Add 1 liter of toluene, add 85 g of potassium tert-butoxide, and heat to reflux until the potassium t...

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Abstract

The invention discloses a method for preparing talipexole (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazole [4,5-d]-aza-dihydrochloride). The method comprises the following steps: using ethyl acrylate as starting raw materials; firstly, carrying out addition reaction on the ethyl acrylate and allyl to generate 3-allylamine base ethyl propionate, then reacting with 4-bromobutyrate to generate 4-(allyl(3-ethoxyl-3-oxopropyl)amino) ethyl butyrate; performing the ring closing reaction under the condition of strong base, decarboxylasing under strong acid to generate 1-allyl azacycloheptane-4-ketone;then performing the nuclear bromination to generate 1-allyl-5-bromine azacycloheptane-4-ketone, and finally, reacting with thiourea to generate a target product (formula I). The invention has novel process, short procedures, high reaction yield, low production cost, and larger implementation value and social and economic benefits.

Description

Technical field [0001] The invention relates to a chemical synthesis method, in particular to a talixol (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazole[4,5-d]-nitrogen Heterodihydrochloride) preparation method. technical background [0002] Talixol (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazole[4,5-d]-azadihydrochloride) is a selective dopamine D2 Receptor agonists can inhibit the release of dopamine in the uninjured area of ​​dopamine nerve endings and reduce dopaminergic nerve conduction, that is, by selectively stimulating dopamine D2 receptors in the postsynaptic membrane of the striatum, thereby producing an anti-Parkinson effect. [0003] Talixol’s first manufacturer was Boehringer Ingelheim, Germany, in 1992, and was officially launched in 1996 as a treatment for Parkinson’s disease. Its structural formula is [0004] [0005] There are not many reports on the preparation method of talixol. Its representative method is the addition of ethyl acrylate and benzylamine to gene...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D513/04A61P25/16
Inventor 高强薛吉军曾亮侯福良郑保富
Owner SHANGHAI HAOYUAN MEDCHEMEXPRESS CO LTD
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