阅读说明：本技术 一种盐酸坦索罗辛晶型的制备方法 (Preparation method of tamsulosin hydrochloride crystal form ) 是由 周健 张伟 胡锦芳 于 2021-01-08 设计创作，主要内容包括：本发明涉及有机化合物的晶型制备技术领域,尤其涉及一种盐酸坦索罗辛晶型的制备方法。该方法在60～70℃的条件下使坦索罗辛完全溶解在溶剂中,然后滴加酸反应一段时间,冷却至20～30℃,过滤,洗涤干燥即得；其中坦索罗辛为精制品。本方法工艺简单,收率高,产品纯度高,适合大规模工业化。(The invention relates to the technical field of preparation of crystal forms of organic compounds, in particular to a preparation method of a tamsulosin hydrochloride crystal form. The method comprises the steps of completely dissolving tamsulosin in a solvent at the temperature of 60-70 ℃, then dropwise adding acid to react for a period of time, cooling to 20-30 ℃, filtering, washing and drying to obtain the tamsulosin; wherein tamsulosin is a refined product. The method has simple process, high yield and high product purity, and is suitable for large-scale industrialization.)

1. A preparation method of tamsulosin hydrochloride crystal form is characterized by comprising the following steps: dissolving tamsulosin in a solvent at 30-85 ℃, then dropwise adding acid into the clear solution, reacting for 1-25 h, cooling to 20-30 ℃, stirring for 1-25 h, filtering, washing and drying to obtain the tamsulosin.

2. The method for preparing tamsulosin hydrochloride crystal forms according to claim 1, wherein the solvent is one or more of acetonitrile, ethanol, acetone, tetrahydrofuran.

3. The method for preparing tamsulosin hydrochloride crystal forms according to claim 1, wherein the acid is one or more of concentrated hydrochloric acid, acetic acid and citric acid.

4. The method for preparing tamsulosin hydrochloride crystal forms according to claim 1, wherein the reaction time is 1-20 hours.

5. The method for preparing tamsulosin hydrochloride crystal forms according to claim 1, wherein the stirring time is 1-20 hours.

6. The method for preparing tamsulosin hydrochloride crystal form according to claim 1, wherein the stirring speed is 100 to 400 rpm.

Technical Field

The invention relates to the field of compound crystal form preparation, in particular to a preparation method of a crystal form of tamsulosin hydrochloride.

Background

Tamsulosin Hydrochloride (Tamsulosin Hydrochloride) is a third-generation selective long-acting alpha 1-adrenoceptor antagonist, developed by pharmaceutical research in japan and approved by FDA in 1992 in month 7. Under the trade name Harnal (Hale). The medicine can specifically inhibit the contraction of prostate smooth muscle, quickly relieve the clinical symptoms of benign prostatic hyperplasia, and has good curative effect and less adverse reactions. Its chemical nomenclature is: 5- [ (2R) -2- [ (2-ethoxyphenoxy) ethyl ] amino ] propyl ] -2-methoxybenzenesulphonamide hydrochloride formula is:

the solid compound forms different crystal form solid states due to different arrangement forms and symmetry rules of molecules of the solid compound; different crystal forms may have different solubilities, and the dissolution rate and stability of the crystal forms may be affected after the crystal forms are prepared into a certain dosage form, so that the clinical curative effect and the quality of the medicine are affected.

The crystal form disclosed in patent CN10410369A shows characteristic peaks of 2 theta angle of 8.56, 13.61, 15.385, 17.25, 18.68 and 22.85.

Disclosure of Invention

The invention aims to provide a preparation method of tamsulosin hydrochloride crystal form, which has simple process, high yield and high product purity and is suitable for large-scale industrial production.

The technical scheme adopted for solving the technical problems comprises the following steps: a preparation method of tamsulosin hydrochloride crystal forms comprises the steps of adding tamsulosin into a solvent, dissolving at 30-85 ℃, then dropwise adding acid into a clear solution, reacting for 1-25 h, cooling to 20-30 ℃, stirring for 1-25 h, filtering, washing and drying to obtain the tamsulosin hydrochloride crystal forms; wherein tamsulosin is a refined product.

Preferably, the solvent is used for dissolving at the temperature of 30-85 ℃, and the solvent is one or more of acetonitrile, ethanol, acetone and tetrahydrofuran.

Preferably, the invention uses acetonitrile to dissolve at 30-85 ℃.

Preferably, acetonitrile is used for dissolving at the temperature of 60-70 ℃, and concentrated hydrochloric acid is dripped.

Preferably, the reaction time is preferably 1-2 h.

Preferably, the stirring speed is 250 rpm.

Preferably, the crystallization time is preferably 4-5 h.

Compared with the prior art, the invention has the beneficial effects that: experiments show that the tamsulosin hydrochloride prepared by the method has the optical purity of 99.9 and the yield of 96 percent, and is suitable for large-scale industrial production.

Drawings

Fig. 1 is an XRD pattern of tamsulosin hydrochloride crystal form provided by the present invention;

fig. 2 is a DSC diagram of tamsulosin hydrochloride crystal form provided by the present invention.

Detailed Description

In order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the invention is further described with the specific embodiments.

Example 1: adding 5g (1.0eq) of tamsulosin into a reaction bottle, adding acetonitrile (10V), heating to 60-70 ℃, dropwise adding concentrated hydrochloric acid (1.5eq) into the reaction solution after complete dissolution, and carrying out heat preservation reaction for 1 h; slowly cooling to about 25 ℃ and stirring for 5 hours; filtration and drying gave 5.17g of a white solid with a purity (HPLC) of 99.98% and a yield of 95%.

Example 2: adding 5g (1.0eq) of tamsulosin into a reaction bottle, adding ethanol (10V), heating to 70-75 ℃, dropwise adding concentrated hydrochloric acid (1.5eq) into the reaction solution after complete dissolution, and reacting for 1h under heat preservation; slowly cooling to about 25 ℃ and stirring for 5 hours; filtration and drying gave 4.95g of a white solid. The purity (HPLC) was 99.89% and the yield was 91%.

Example 3: adding 5g (1.0eq) of tamsulosin into a reaction bottle, adding acetone (15V), heating to 50-55 ℃, after complete dissolution, dropwise adding concentrated hydrochloric acid (1.5eq) into the reaction solution, and keeping the temperature for reaction for 1 h; slowly cooling to about 25 ℃ and stirring for 5 hours; filtration and drying gave 5.28g of a white solid. The purity (HPLC) was 99.80% and the yield was 97%.

Example 4: adding 100g (1.0eq) of tamsulosin into a reaction bottle, adding acetonitrile (10V), heating to 60-70 ℃, after complete dissolution, dropwise adding concentrated hydrochloric acid (1.5eq) into the reaction solution, and keeping the temperature for reaction for 1 h; slowly cooling to about 25 ℃ and stirring for 5 hours; filtration and drying gave 104.6g of a white solid. The purity (HPLC) was 99.96% and the yield was 96%.

Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.