WO2010015169A1 - 一种依普罗沙甲磺酸盐的制备方法 - Google Patents

一种依普罗沙甲磺酸盐的制备方法 Download PDF

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WO2010015169A1
WO2010015169A1 PCT/CN2009/072832 CN2009072832W WO2010015169A1 WO 2010015169 A1 WO2010015169 A1 WO 2010015169A1 CN 2009072832 W CN2009072832 W CN 2009072832W WO 2010015169 A1 WO2010015169 A1 WO 2010015169A1
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eprosartan
acetic acid
glacial acetic
eprosartan mesylate
mesylate
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PCT/CN2009/072832
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French (fr)
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黄想亮
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浙江华海药业股份有限公司
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Priority to CN2009801078091A priority Critical patent/CN101959880B/zh
Priority to EP09804469A priority patent/EP2305670A4/en
Priority to US12/989,765 priority patent/US8546585B2/en
Publication of WO2010015169A1 publication Critical patent/WO2010015169A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

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  • the present invention relates to a salt forming process of a pharmaceutical compound eprosartan mesylate, which belongs to the field of medicine and chemical industry.
  • Eprosartan Mesylate was successfully developed by Schiphol in 1997 and was launched in Germany in 1998 under the trade name Teveten. It was later listed in the US in 1999.
  • Eprosartan mesylate an angiotensin II receptor blocker
  • Eprosartan mesylate is the latest generation of antihypertensive drugs that reduce systolic and diastolic blood pressure in patients with mild, moderate, and severe hypertension. Both have curative effect, and have good safety and tolerance.
  • the oral absorption is rapid, the bioavailability is 13%, the protein binding rate is 98%, the liver and kidney dysfunction or taking this product after eating, blood
  • the peak drug concentration and AUC can be increased by about 50%, and can be increased by 2 to 3 times for elderly patients.
  • the structural formula of eprosartan mesylate is as follows:
  • U.S. Patent No. 5,185,351 discloses the preparation of eprosartan mesylate in isopropanol with eprosartan and methanesulfonic acid (US 5,185,351, Example 41 (ii)), but industrially using this method to prepare eprosar In the case of tannsulfonate, it was found that the esterification of eprosartan with isopropanol produced the following two impurities:
  • the salt-forming method provided by the above patents is extremely easy to form isopropyl methanesulfonate in addition to the two esterification impurities. Based on the current potential toxicity of mesylate to human genotoxicity and the strict requirements of mesalates in Europe and the Americas, the method of using mesylate in non-alcoholic solvents in the production of eprosartan mesylate is equivalent. Important, because this avoids the formation of mesylate and the residue in the finished product. Due to the high dose of eprosartan mesylate, it is particularly important to strictly control the mesylate in eprosartan mesylate.
  • the above salt-forming method suspends eprosartan solid in isopropanol at a low temperature, and after about ten seconds after the addition of methanesulfonic acid, a large amount of eprosartan mesylate is precipitated, and eprosartan is present.
  • the solid precipitated eprosartan mesylate was embedded in the image. Since isopropyl alcohol has a high viscosity at a low temperature, the amount of hydrazine filtration required to obtain a solid from isopropyl alcohol is large, and the amount of isopropyl alcohol solvent contained in the solid is large.
  • the invention overcomes the formation of isopropyl methanesulfonate and eprosartan isopropyl ester in the preparation process of eprosartan mesylate, provides an operation tube, is suitable for industrial production, economical, effective and capable A method for preparing eprosartan mesylate in high yield and high purity.
  • the inventors of the present application have found through repeated experiments that eprosartan is suspended or dissolved in glacial acetic acid, and methanesulfonic acid is added to obtain a clear glacial acetic acid solution of eprosartan mesylate, which is stirred for about 1 hour.
  • the eprosartan mesylate solid was slowly precipitated, so that the salt of eprosartan and methanesulfonic acid was not embedded; the ethyl acetate was added to make the eprosartan mesylate crystallized sufficiently, and the obtained solid was extremely easy.
  • the resulting wet product has a low solvent content and is therefore easy to dry.
  • the new process of adding the methanesulfonic acid salt to glacial acetic acid with eprosartan will not only produce new impurities, but also reduce the original impurities to a certain extent.
  • the technical scheme adopted by the invention is as follows: Dissolving or suspending eprosartan in glacial acetic acid, adding methanesulfonic acid, stirring to obtain a glacial acetic acid solution of eprosartan mesylate, and continuously extracting solids and then filtering to obtain Prosalazine mesylate solid, or concentrated glacial acetic acid to dry to obtain eprosartan mesylate solid, or dropwise addition of organic ester solvent in glacial acetic acid, stirring and crystallization, separation of eprosartan methyl sulfonate Acid salt solid.
  • reaction formula The reaction to which the present invention relates can be expressed by the following reaction formula:
  • Eprosartan Eprosartan Mesylate In the reaction of the present invention, eprosartan can be suspended in glacial acetic acid, or heated to partially dissolve or completely dissolved in glacial acetic acid, and then added with methanesulfonic acid, preferably suspended in glacial acetic acid to add methanesulfonic acid.
  • the ratio of the amount of glacial acetic acid (m 1 ) to the mass (g) of eprosartan in the reaction of the present invention is preferably from 3 to 4 ml/g.
  • the ratio of the amount (g) of eprosartan to the methanesulfonic acid (g) is preferably 1:0.3 to 0.5.
  • the reaction temperature of the methanesulfonic acid salt of the present invention is from 10 ° C to 110 ° C, preferably from 25 ° C to 35 ° C; and the reaction time is from 5 minutes to 3 hours, preferably from 0.5 hour to 1 hour.
  • the method for separating eprosartan mesylate according to the present invention is to use a continuous stirring to precipitate a solid, and then filtering to obtain an eprosartan mesylate solid; or concentrating glacial acetic acid to dryness and then adding an organic ester solvent to wash; or The organic ester solvent was added dropwise to the glacial acetic acid to stir and crystallize, and the eprosartan solid was isolated.
  • the organic ester solvent to be added is a C3 ⁇ C10 ester, which may be ethyl acetate, isopropyl acetate or n-butyl acetate, which is added in an amount of 30 times (ml/g) of the quality of eprosartan. It is 6 fly times (ml/g); wherein the preferred solvent is ethyl acetate.
  • Eprosartan was suspended in glacial acetic acid in a volume of 3 to 4 times (ml/g) of eprosartan, stirred at room temperature for 5 to 10 minutes, and then added with the mass of eprosartan 0.3 times (i) For methanesulfonic acid, immediately obtain a clear liquid, continue to stir for about 1 hour, add 6 to 8 times (ml / g) of ethyl acetate in a volume of eprosartan, and continue stirring for 3 to 5 hours after the addition. After suction filtration, vacuum drying at 50 ° C gave an off-white eprosartan mesylate.
  • the method provided by the invention avoids the formation of isopropyl methanesulfonate, so that there is no nail in the finished product. Isopropyl sulfonate impurity;
  • the invention provides a method for operating the cartridge, the yield is stable, and the drying is easy;
  • the product obtained by the method of the present invention has high purity and requires no further purification, i.e., meets the product requirements. detailed description

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Description

一种依普罗沙甲磺酸盐的制备方法
本申请要求于 2008 年 8 月 3 日提交中国专利局、 申请号为 200810129646.4, 发明名称为 "一种新的依普罗沙坦甲磺酸盐成盐工艺" 的中 国专利申请的优先权， 其全部内容通过引用结合在本申请中。
技术领域 本发明涉及一种药物化合物依普罗沙坦甲磺酸盐的成盐工艺，属医药化工 领域。
背景技术
依普罗沙坦甲横酸盐 （Eprosartan Mesylate ) 由史克必成公司于 1997 年开发成功， 1998年在德国上市， 商品名 Teveten, 以后于 1999年在美国上 市。 依普罗沙坦甲磺酸盐是血管紧张素 II受体阻断剂， 是最新一代的抗高血 压药物， 该药对于轻度、 中度和严重高血压病人在降低心脏收缩压和心脏舒张 压两方面都有疗效，且具有良好的安全性及耐受性， 其口服吸收迅速， 生物利 用度为 13%, 蛋白结合率为 98% , 肝肾功能不全者或饱食后服用本品， 血药 浓度峰值和 AUC均可增加约 50 % , 对老年病人可增加 2 ~ 3倍。 依普罗沙坦甲 磺酸盐结构式如下：
Figure imgf000003_0001
Eprosartan Mesylate
美国专利 US5185351 公开了依普罗沙坦与甲磺酸在异丙醇中制备依普罗 沙坦甲磺酸盐的方法（US5185351 , Example 41 (i i) ), 但在工业上采用此方法 制备依普罗沙坦甲磺酸盐时发现，依普罗沙坦与异丙醇发生酯化反应生成如下 两个杂质：
Figure imgf000003_0002
异丙酯化杂质 1 异丙酯化杂质 2
上述专利提供的成盐方法除生成两酯化杂质外，还极易生成甲磺酸异丙酯。基 于目前甲磺酸酯对人体基因毒性的潜在危险以及欧洲、美洲官方对甲磺酸酯的 严格要求，依普罗沙坦甲磺酸生产过程中采用非醇溶剂中成甲磺酸盐的方法相 当重要， 因为这样避免甲磺酸酯的生成以及在成品中的残留。 由于甲磺酸依普 罗沙坦剂量大， 严格控制依普罗沙坦甲磺酸盐中的甲磺酸酯尤为重要。
此外， 上述成盐方法在低温下将依普罗沙坦固体悬浮于异丙醇中，加入甲 磺酸后约十秒后即得到依普罗沙坦甲磺酸盐大量沉淀，存在着依普罗沙坦固体 被沉淀出来的依普罗沙坦甲磺酸盐包埋现像。 由于异丙醇在低温下粘度大，从 异丙醇中得到固体所需要的甩滤工作量大， 且固体中含异丙醇溶剂量大。 发明内容
本发明克服了依普罗沙坦甲磺酸盐制备过程中甲磺酸异丙酯及依普罗沙 坦异丙酯杂质的生成， 提供了一种操作筒便， 适合工业生产， 经济， 有效且能 够高收率， 高纯度地制备依普罗沙坦甲磺酸盐的方法。
本申请发明人经过多次实验发现， 将依普罗沙坦悬浮或溶解于冰乙酸中， 加入甲磺酸， 得到澄清的依普罗沙坦甲磺酸盐的冰乙酸溶液， 搅拌约 1小时后 可緩慢析出依普罗沙坦甲磺酸盐固体，这样依普罗沙坦与甲磺酸成盐没有包埋 现象； 加入乙酸乙酯使依普罗沙坦甲磺酸盐析晶充分，得到的固体极易抽滤至 干， 所得到的湿品中溶剂含量很低， 从而易于干燥。 此外， 采用依普罗沙坦在 冰乙酸中加入甲磺酸成盐的新工艺， 不仅不会产生新的杂质， 而且原有杂质会 有一定程度的下降。
本发明采用的技术方案为： 将依普罗沙坦溶解或悬浮于冰乙酸中，加入甲 磺酸后搅拌得到依普罗沙坦甲磺酸盐的冰乙酸溶液，采用继续搅拌析出固体后 过滤得到依普罗沙坦甲磺酸盐固体，或采用浓缩冰乙酸至干得到依普罗沙坦甲 磺酸盐固体，或在冰乙酸中滴加有机酯类溶剂搅拌析晶后分离得到依普罗沙坦 甲磺酸盐固体。 其中， 依普罗沙坦（质量 g ): 甲磺酸盐（质量 g) : 冰乙酸 (体积 ml) =l: 0. 1 ~ 5. 0: 1 ~ 15 , 反应温度为 10 °C ~ 110 °C。
本发明所涉及到的反应可以用如下的反应式来表示：
Figure imgf000004_0001
Eprosartan Eprosartan Mesylate 本发明所述反应中依普罗沙坦可以悬浮于冰乙酸中，或加热至部分溶解或 全部溶解于冰乙酸后再加入甲磺酸， 优选为悬浮于冰乙酸中加入甲磺酸。
本发明所述反应中冰乙酸的用量（m 1 )与依普罗沙坦质量（ g )比优选为 3 ~ 4ml/g。 依普罗沙坦的用量（g)与甲磺酸 （g)的比优选为 1: 0.3 ~ 0.5。
本发明所述甲磺酸成盐的反应温度为 10°C ~ 110°C, 优选为 25°C ~ 35°C; 反应时间为 5分钟至 3小时， 优选为 0.5小时至 1小时。
本发明所述的分离依普罗沙坦甲磺酸盐的方法为采用继续搅拌析出固体 后过滤得到依普罗沙坦甲磺酸盐固体；或浓缩冰乙酸至干后加入有机酯类溶剂 洗涤； 或在冰乙酸中滴加入有机酯类溶剂搅拌析晶后分离得到依普罗沙坦固 体。 其中加入的有机酯类溶剂为 C3~C10的酯， 可以为乙酸乙酯、 乙酸异丙酯、 乙酸正丁酯， 其加入量为依普罗沙坦质量的厂 30倍 （ml/g ), 优选为 6飞倍 (ml/g); 其中优选的溶剂为乙酸乙酯。
推荐所述的制备方法可按照如下步骤即可：
将依普罗沙坦悬浮于体积用量为依普罗沙坦 3 ~4倍（ml/g) 的冰乙酸中， 室温下搅拌 5至 10分钟， 然后加入质量为依普罗沙坦 0.3倍的（ i )的甲磺酸， 立即得到澄清液， 继续搅拌约 1小时， 滴加入体积用量为依普罗沙坦 6 ~ 8倍 (ml/g) 的乙酸乙酯， 滴加完毕后继续搅拌 3 ~ 5小时， 抽滤， 50°C真空干燥， 即得到类白色依普罗沙坦甲磺酸盐。
与现有技术相比， 本发明的优点在于：
1、 避免现有技术中成盐工艺产生的异丙酯杂质， 此异丙酯杂质在后续过 程中通过重结晶方法除去非常困难；
2、 本发明所提供的方法避免了甲磺酸异丙酯的生成， 从而成品中没有甲 磺酸异丙酯杂质；
3、 本发明提供方法操作筒单， 收率稳定， 易于干燥；
4、 本发明所提供的方法得到的产物纯度高， 无需进一步精制， 即达到成 品要求。 具体实施方式
下面以具体实施例来进一步说明本发明的技术方案，但本发明的保护范围 不限于此： 实施例一
500mL茄形瓶中加入 31. 8 g依普罗沙坦和 128mL冰乙酸，室温下搅拌 10分钟， 加入 9. 4g甲磺酸， 反应液迅速变澄清，继续搅拌约 lh后开始析出白色固体， 继 续搅拌约 5小时， 抽滤， 50 °C真空干燥， 得 22. 6g类白色固体， 收率 58%。 实施例二
500mL茄形瓶中加入 31. 8 g依普罗沙坦和 222mL冰乙酸， 加热至 75 °C搅拌溶 清，加入 10. 8g甲磺酸， 继续搅拌 2h, 冷却， 浓缩至干，加入 300mL乙酸异丙酯， 室温下搅拌 3小时， 抽滤后 50 °C真空干燥， 得 34. 9g类白色固体， 收率 89. 5%。 实施例三
500mL茄形瓶中加入 31. 8 g依普罗沙坦和 222mL冰乙酸， 加热至 75 °C搅拌溶 清， 加入 1 0. 8g甲磺酸， 继续搅拌 lh, 冷却至室温， 滴加入 300mL乙酸正丁酯， 滴加完毕后室温下搅拌 3小时， 抽滤后 50°C真空干燥， 得 32.7g类白色固体， 收 率 83. n。 实施例四
500mL茄形瓶中加入 31.8g依普罗沙坦和 128mL冰乙酸， 加热至 110°C回流， 搅拌溶清， 稍冷后加入 9.4g甲磺酸， 继续搅拌 2h, 冷却， 浓缩至干， 加入 300mL 乙酸乙酯， 室温下搅拌 3小时， 抽滤后 50°C真空干燥， 得 34. Og类白色固体， 收 率 87.2%。 实施例五
500mL茄形瓶中加入 31.8g依普罗沙坦和 128mL冰乙酸，室温下搅拌 10分钟， 加入 9.4g甲磺酸， 反应液迅速变澄清，继续搅拌 2h, 浓缩至干， 加入 200mL乙酸 乙酯， 室温下搅拌 3小时， 抽滤后湿重 35.6g， 50°C真空干燥， 得 33.7g类白色固 体， 收率 86.4%, 纯度 99.8%。 实施例六
500mL茄形瓶中加入 20. Og依普罗沙坦和 80mL冰乙酸， 室温下搅拌 10分钟， 加入 5.9g甲磺酸， 反应液迅速变澄清，继续搅拌 lh, 滴加入 200mL乙酸乙酯， 滴 加完毕后室温下搅拌 3小时， 抽滤后湿重 19.6g， 50°C真空干燥， 得 20.5g类白 色固体， 收率 83.7%, 纯度 99.8%。 实施例七 l OOOmL茄形瓶中加入 25. Og依普罗沙坦和 300mL冰乙酸， 室温下搅拌约 10 分钟， 加入 9. 4g甲磺酸， 继续搅拌 lh , 滴加入 600mL乙酸乙酯， 室温下搅拌 3 小时， 抽滤后 50 °C真空干燥， 得 23. 8g类白色固体， 收率 76. 8%。 实施例八
500mL茄形瓶中加入 25. Og依普罗沙坦和 75mL冰乙酸， 室温下搅拌 10分钟， 加入 7. 4g甲磺酸， 反应液迅速变澄清，继续搅拌 2h, 滴加入 420mL乙酸乙酯， 室 温下搅拌 3小时， 抽滤后 50 °C真空干燥， 得 26. 4g类白色固体， 收率 86. 0%, 纯 度 99. 8%。 以上对本发明所提供的技术方案进行了详细介绍。本说明书中应用了具体 实施例对本发明的原理及实施方式进行了阐述， 对于本领域的一般技术人员， 依据本发明的思想在具体实施方式及应用范围上可能在实施过程中会有改变 之处。 因此， 本说明书记载的内容不应理解为对本发明的限制。

Claims

权 利 要 求
1、 一种依普罗沙坦甲磺酸盐成盐工艺， 其特征在于： 将依普罗沙坦溶解 或悬浮于冰乙酸中， 加入甲磺酸后搅拌得到依普罗沙坦甲磺酸盐的冰乙酸溶 液， 采用继续搅拌析出固体后过滤得到依普罗沙坦甲磺酸盐固体，或采用浓缩 冰乙酸至干得到依普罗沙坦甲磺酸盐固体，或在冰乙酸中滴加有机酯类溶剂搅 拌析晶后分离得到依普罗沙坦甲磺酸盐固体。
2、根据权利要求 1所述的依普罗沙坦甲磺酸盐成盐工艺， 其特征在于依普 罗沙坦可以悬浮于冰乙酸中 ,或加热至部分溶解或全部溶解于冰乙酸后再加入 甲磺酸， 优选为悬浮于冰乙酸中加入甲磺酸。
3、根据权利要求 1所述的依普罗沙坦甲磺酸盐成盐工艺， 其特征在于依普 罗沙坦（质量 g): 甲磺酸盐（质量 g): 冰乙酸（体积 ml)=l: 0.1 ~5.0: 1 ~ 15。
4、根据权利要求 3所述的依普罗沙坦甲磺酸盐成盐工艺， 其特征在于所述 依普罗沙坦质量（g) 与冰乙酸的用量（ml)的比优选为 1: 3~4；依普罗沙坦（g) 与甲磺酸的用量（g)比优选为 1: 0.3-0.50
5、根据权利要求 1所述的依普罗沙坦甲磺酸盐成盐工艺， 其特征在于所述 甲磺酸成盐的反应温度为 10°C ~ 110°C, 优选为 25°C ~ 35°C。
6、根据权利要求 1所述的依普罗沙坦甲磺酸盐成盐工艺，加入甲磺酸后反 应时间为 5分钟至 3小时， 优选为 0.5小时 ~ 1小时。
7、根据权利要求 1所述的依普罗沙坦甲磺酸盐成盐工艺， 其特征在于加入 的有机酯类溶剂为 C 3 ~ C 10的酯， 优选为乙酸乙酯。
8、根据权利要求 7所述的依普罗沙坦甲磺酸盐成盐工艺，其特征在于有机 酯类溶剂的加入量为依普罗沙坦质量的 1 ~ 30倍（ml/g ),优选为 6 ~ 8倍（ml/g )。
PCT/CN2009/072832 2008-08-03 2009-07-20 一种依普罗沙甲磺酸盐的制备方法 WO2010015169A1 (zh)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5185351A (en) 1989-06-14 1993-02-09 Smithkline Beecham Corporation Imidazolyl-alkenoic acids useful as angiotensin II receptor antagonists
WO1997036874A1 (en) * 1996-03-29 1997-10-09 Smithkline Beecham Corporation Eprosartan dihydrate and a process for its production and formulation
WO2008078330A1 (en) * 2006-12-27 2008-07-03 Hetero Drugs Limited Improved process for eprosartan
WO2009084028A2 (en) * 2007-12-03 2009-07-09 Neuland Laboratories Ltd Improved process for manufacturing anhydrous (e)-3-[2-butyl-1- {(4-carboxyphenyl) methyl}-1h-imidazole-5-yl]-(thiophen-2- ylmethyl)prop-2-enoic acid methane sulfonate

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009013760A2 (en) 2007-07-25 2009-01-29 Hetero Drugs Limited Eprosartan mesylate crystalline particles and a process for preparing pure eprosartan

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5185351A (en) 1989-06-14 1993-02-09 Smithkline Beecham Corporation Imidazolyl-alkenoic acids useful as angiotensin II receptor antagonists
WO1997036874A1 (en) * 1996-03-29 1997-10-09 Smithkline Beecham Corporation Eprosartan dihydrate and a process for its production and formulation
WO2008078330A1 (en) * 2006-12-27 2008-07-03 Hetero Drugs Limited Improved process for eprosartan
WO2009084028A2 (en) * 2007-12-03 2009-07-09 Neuland Laboratories Ltd Improved process for manufacturing anhydrous (e)-3-[2-butyl-1- {(4-carboxyphenyl) methyl}-1h-imidazole-5-yl]-(thiophen-2- ylmethyl)prop-2-enoic acid methane sulfonate

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP2305670A4 *

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