CN114621188A - 一种泮托拉唑的制备方法 - Google Patents

一种泮托拉唑的制备方法 Download PDF

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Publication number
CN114621188A
CN114621188A CN202011453896.0A CN202011453896A CN114621188A CN 114621188 A CN114621188 A CN 114621188A CN 202011453896 A CN202011453896 A CN 202011453896A CN 114621188 A CN114621188 A CN 114621188A
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pantoprazole
preparation
stirring
difluoromethoxy
benzimidazole
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魏阿倩
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Nanjing Polytechnic Institute
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Nanjing Polytechnic Institute
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

本发明涉及一种泮托拉唑的制备技术领域，特别涉及由2‑巯基‑5‑二氟甲氧基‑1H‑苯并咪唑和2‑氯甲基‑3，4‑二甲氧基吡啶盐酸盐缩合，再用间氯过苯甲酸氧化来制备的方法。

Description

一种泮托拉唑的制备方法
技术领域
本发明涉及一种泮托拉唑的制备技术领域，特别涉及由2-巯基-5-二氟甲氧基-1H-苯并咪唑和2-氯甲基-3，4-二甲氧基吡啶盐酸盐缩合，再用间氯过苯甲酸氧化来制备的方法。
背景技术
泮托拉唑，又名5-二氟甲氧基-2-[(3,4-二甲氧基-2-吡啶基)甲基]亚硫酰基-1H-苯并咪唑，常温下为近乎白色的固体。临床上是一种质子泵抑制剂药物，抑制胃酸分泌。用于治疗活动性消化性溃疡反流性食管炎和卓一艾氏综合症。
发明内容
本发明的目的在于提供一种泮托拉唑的制备方法。
本发明采用的技术方案为：
1. 2-巯甲基-3,4-二甲氧基吡啶的制备
在反应瓶中加入2-氯甲基-3,4-二甲氧基吡啶盐酸盐22.8g、硫脲9.1g和95%乙醇120ml,搅拌回流3h.冷却,再加入2mol/LKOH水溶液120ml,于室温搅拌10h.冷却,反应液用氯仿提取,有机相用无水MgSO4干燥,过滤,滤液减压浓缩,得白色固体2-巯甲基-3,4-二甲氧基吡啶15.4g,mp113~115ºC.
2. (3,4-二甲氧基吡啶-2-基)甲硫基甲酸乙酯的制备
在反应瓶中加入2-巯甲基-3,4-二甲氧基吡啶9.5g和二氯甲烷100ml,搅拌溶解,冷却至0ºC,加入氯甲酸乙酯5.7ml和三乙胺8.4ml,室温搅拌5h.反应液用水洗,有机相用无水MgSO4干燥,过滤,滤液减压浓缩得黄色油状物(3,4-二甲氧基吡啶-2-基)甲硫基甲酸乙酯11.8g.
3. 5-二氟甲氧基-2-[(3,4-二甲氧基吡啶-2-基)甲硫基]-1H-苯并咪唑的制备
在反应瓶中加入(3,4-二甲氧基吡啶-2-基)甲硫基甲酸乙酯12.6g、5-二氟甲氧基邻苯二胺12.4g和甲苯100ml,搅拌回流5h.冷却至5ºC以下,析出结晶,抽滤,用甲苯洗涤,抽干,干燥得白色固体5-二氟甲氧基-2-[(3,4-二甲氧基吡啶-2-基)甲硫基]-1H-苯并咪唑16.2g,mp118~119ºC.
4. 泮托拉唑的合成
在反应瓶中加入5-二氟甲氧基-2-[(3,4-二甲氧基吡啶-2-基)甲硫基]-1H-苯并咪唑7.4g和二氯甲烷100ml,于冰水浴冷却下,搅拌加入间氯过氧苯甲酸3.5g,室温搅拌反应5h.用10%K2CO3水溶液洗涤,有机相用无水MgSO4干燥,过滤,滤液蒸除溶剂,剩余物用异丙醇重结晶,得白色固体5-(二氟甲氧基)-2-[[(3-二甲氧基-2-吡啶基)甲基]亚磺酰基]-1H-苯并咪唑泮托拉唑7.0g,mp138~139ºC(分解).
本发明的主要优点是：工艺简单，反应温度低，反应时间短；产品产率高，纯度高。
具体实施方式
为了更详细地说明本发明的特点，下面通过具体的实施实例对本发明作进一步的阐述，而不是限制本发明的范围。
实施例1：
在反应瓶中加入2-氯甲基-3,4-二甲氧基吡啶盐酸盐22.8g、硫脲9.1g和95%乙醇120ml,搅拌回流3h.冷却,再加入2mol/LKOH水溶液120ml,于室温搅拌10h.冷却,反应液用氯仿提取,有机相用无水MgSO4干燥,过滤,滤液减压浓缩,得白色固体2-巯甲基-3,4-二甲氧基吡啶15.4g,mp113~115ºC。
实施例2：
在反应瓶中加入2-巯甲基-3,4-二甲氧基吡啶9.5g和二氯甲烷100ml,搅拌溶解,冷却至0ºC,加入氯甲酸乙酯5.7ml和三乙胺8.4ml,室温搅拌5h.反应液用水洗,有机相用无水MgSO4干燥,过滤,滤液减压浓缩得黄色油状物(3,4-二甲氧基吡啶-2-基)甲硫基甲酸乙酯11.8g。在反应瓶中加入5-二氟甲氧基-2-[(3,4-二甲氧基吡啶-2-基)甲硫基]-1H-苯并咪唑7.4g和二氯甲烷100ml,于冰水浴冷却下,搅拌加入间氯过氧苯甲酸3.5g,室温搅拌反应5h.用10%K2CO3水溶液洗涤,有机相用无水MgSO4干燥,过滤,滤液蒸除溶剂,剩余物用异丙醇重结晶,得白色固体5-(二氟甲氧基)-2-[[(3-二甲氧基-2-吡啶基)甲基]亚磺酰基]-1H-苯并咪唑泮托拉唑7.0g,mp138~139ºC(分解)。

Claims (1)

1.一种泮托拉唑的制备方法，其特征在于：
本发明涉及一种泮托拉唑的制备技术领域，特别涉及由2-巯基-5-二氟甲氧基-1H-苯并咪唑和2-氯甲基-3，4-二甲氧基吡啶盐酸盐缩合，再用间氯过苯甲酸氧化来制备的方法。
CN202011453896.0A 2020-12-12 2020-12-12 一种泮托拉唑的制备方法 Pending CN114621188A (zh)

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