Method for preparing iloperidone

A technology of iloperidone and ethyl ketone, applied in the field of preparation of iloperidone, can solve the problem of affecting the efficacy of iloperidone preparations, affecting the yield and purity of iloperidone, and being difficult to remove by-products, etc. question

Inactive Publication Date: 2011-10-12
北京美迪康信医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] The method adopts the reaction of 4-hydroxy-3-methoxyacetophenone and 1-bromo-3-chloropropane, and the obtained by-product is difficult to remove in t

Method used

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  • Method for preparing iloperidone
  • Method for preparing iloperidone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] (1) Preparation of 3-[1-(3-chloropropyl)piperidin-4-yl]-6-fluoro-1,2-phenylpropisoxazole

[0022] Mix 68g of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride, 22g of sodium hydroxide and 400ml of acetonitrile completely, and add 54g of 1- Bromo-3-chloropropane and 40ml of acetonitrile were incubated and stirred for 12 hours, then the mixture was poured into water at 0°C with stirring, filtered to obtain a solid, and dried to obtain 70g of 3-[1-(3-chloropropyl)piperidine -4-yl]-6-fluoro-1,2-phenylisoxazole, yield 89.1%;

[0023] (2) Preparation of iloperidone

[0024] 70g 3-[1-(3-chloropropyl)piperidin-4-yl]-6-fluoro-1,2-phenylpropisoxazole, 37.5g sodium carbonate and 600ml isopropanol were mixed completely, at 40 At ℃, add 9g of potassium iodide, 39g of 4-hydroxy-3-methoxyacetophenone and 100ml of isopropanol, react at 40℃ for 35 hours, filter, and concentrate the filtrate to dryness to obtain a semi-solid, which Add 175ml of methanol, heat to dissolve comp...

Embodiment 2

[0027] (1) Preparation of 3-[1-(3-chloropropyl)piperidin-4-yl]-6-fluoro-1,2-phenylpropisoxazole

[0028] 677g 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride, 360g potassium hydroxide and 1200ml N,N-dimethylformamide, 1200ml N,N- Mix dimethylacetamide and 1600ml dimethylsulfoxide completely, add 538g 1-bromo-3-chloropropane and 150ml N,N-dimethylformamide, 150ml N,N-di Methyl acetamide, 100ml dimethyl sulfoxide, heat preservation and stirring for 12 hours, then pour the mixture into water at 5°C with stirring, filter to obtain a solid, dry to obtain 3-[1-(3-chloropropyl)piperene Pyridin-4-yl]-6-fluoro-1,2-phenylisoxazole 708g, yield 90.5%;

[0029] (2) Preparation of iloperidone

[0030] 708g 3-[1-(3-chloropropyl)piperidin-4-yl]-6-fluoro-1,2-phenylpropisoxazole, 98g sodium hydroxide and 3000ml 1,4-dioxane , 3000ml tetrahydrofuran and mixed completely, at 60°C, add 88g sodium iodide, 396g 4-hydroxy-3-methoxyacetophenone and 500ml 1,4-dioxane, 500ml tetrahydrofuran...

Embodiment 3

[0033] (1) Preparation of 3-[1-(3-chloropropyl)piperidin-4-yl]-6-fluoro-1,2-phenylpropisoxazole

[0034]331g of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride, 171g of sodium ethylate and 1200ml of N,N-dimethylacetamide, 800ml of acetonitrile were mixed completely, in At 5-10°C, add 268g of 1-bromo-3-chloropropane, 120ml of N,N-dimethylacetamide, and 80ml of acetonitrile, keep stirring for 8 hours, then pour the mixture into water at 0°C while stirring, and filter. The solid was obtained and dried to obtain 338g of 3-[1-(3-chloropropyl)piperidin-4-yl]-6-fluoro-1,2-phenylpropisoxazole with a yield of 88.5%;

[0035] (2) Preparation of iloperidone

[0036] 338g 3-[1-(3-chloropropyl)piperidin-4-yl]-6-fluoro-1,2-phenylpropisoxazole, 181.2g potassium tert-butoxide and 2900ml acetone were mixed completely, at 50 At ℃, add 44g of potassium iodide, 190g of 4-hydroxy-3-methoxyacetophenone and 500ml of acetone, react at 50℃ for 30 hours, filter, and concentrate the filtrat...

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Abstract

The invention belongs to the technical field of medicines. The invention discloses a method for preparing iloperidone. The method comprises the following steps of: reacting 6-fluoro-3-(4-piperidinyl)-1,2 benzisoxazole monohydrochloride and 1-bromine-3-chloropropane, which are both used as raw materials, to obtain 3-[1-(3-chloropropyl)piperidine-4-radical]-6-fluoro-1,2 benzoisoxazole, and reacting the obtained product and 4-hydroxyl-3-methoxyacetophenone serving as a raw material to obtain the iloperidone. Research shows that the byproducts generated in the method can be easily removed in the purifying process, so that the method has the advantages of high yield, high product purity and the like.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method of iloperidone. Background technique [0002] In recent years, the prevalence of schizophrenia in China has been on the rise. According to the report of the Ministry of Health of my country in 2002, there are about 8 million patients with schizophrenia in my country, and the number of new patients is 150,000 each year. increased to around 8.6 million. The incidence of schizophrenia is high, the age of onset is early, and the conditions leading to disability are also relatively early. According to the above characteristics, schizophrenia is one of the important diseases causing socioeconomic burden. [0003] Antipsychotics generally fall into two categories, first-generation antipsychotics (FGAs; or classic antipsychotics) and second-generation antipsychotics (SGAs; or atypical antipsychotics). The pharmacological effect of the first generation ...

Claims

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Application Information

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IPC IPC(8): C07D413/04
Inventor 谢寅省赵丽云
Owner 北京美迪康信医药科技有限公司
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