CN106565579A - 一种尔它培南侧链生产工艺 - Google Patents

一种尔它培南侧链生产工艺 Download PDF

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Publication number
CN106565579A
CN106565579A CN201610469508.5A CN201610469508A CN106565579A CN 106565579 A CN106565579 A CN 106565579A CN 201610469508 A CN201610469508 A CN 201610469508A CN 106565579 A CN106565579 A CN 106565579A
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China
Prior art keywords
side chain
ertapenem
bacteria
ethyl acetate
solvent
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CN201610469508.5A
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胡天忠
裴红霞
张晓磊
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Ningxia Haicheng Electronic Mdt Infotech Ltd
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Ningxia Haicheng Electronic Mdt Infotech Ltd
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Priority to CN201610469508.5A priority Critical patent/CN106565579A/zh
Publication of CN106565579A publication Critical patent/CN106565579A/zh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

本发明涉及医药制药领域，尤其是尔它培南侧链属于医药制药领域。尔它培南侧链属于医药制药原料，可用于生产尔它培南抗生素药品。尔它培南是一种新型碳青霉烯类抗生素，通过与青霉素结合蛋白结合，干扰细菌细胞壁的合成，导致细菌生长繁殖受抑制，少数出现细胞溶解。该品对甲氧西林敏感金葡菌、肺炎链球菌、化脓性链球菌等革兰阳性菌、肠杆菌科细菌具有高度抗菌活性；嗜血杆菌属、卡他莫拉菌、脑膜炎奈瑟球菌等对该品高度敏感，但对甲氧西林耐药葡萄球菌、肠球菌属、铜绿假单胞菌、不动杆菌属等细菌对该品耐药。

Description

一种尔它培南侧链生产工艺
技术领域
本发明涉及医药制药领域，尤其是尔它培南侧链属于医药制药领域。
背景技术
尔它培南侧链属于医药制药原料，可用于生产尔它培南抗生素药品。尔它培南是一种新型碳青霉烯类抗生素，通过与青霉素结合蛋白结合，干扰细菌细胞壁的合成，导致细菌生长繁殖受抑制，少数出现细胞溶解。该品对甲氧西林敏感金葡菌、肺炎链球菌、化脓性链球菌等革兰阳性菌、肠杆菌科细菌具有高度抗菌活性；嗜血杆菌属、卡他莫拉菌、脑膜炎奈瑟球菌等对该品高度敏感，但对甲氧西林耐药葡萄球菌、肠球菌属、铜绿假单胞菌、不动杆菌属等细菌对该品耐药。
发明内容
工艺流程：向成品酸化釜中真空抽入溶剂冰乙酸，人工投入中间体Q、间氨基苯甲酸，然后采用循环热水升温至35-40℃保温反应3h。反应结束后，采用循环冷却水降至室温，向中泵入溶剂乙酸乙酯，搅拌2h后离心，湿品送入真空干燥烘箱保持40℃烘干后得尔它培南侧链。
该过程间氨基苯甲酸过量，转化率84%；尔它培南侧链的收率为76.14%。冰乙酸、乙酸乙酯作为溶剂使用，离心母液进入溶剂回收系统回收乙酸乙酯和乙酸：先常压下热水加热回收釜温度升高至85℃，回收乙酸乙酯，再减压至-0.098MPa、T=85℃ 回收乙酸。
反应原理：
。

Claims (1)

1.本发明涉及原料成分及配比；
本发明涉及工艺流程：向成品酸化釜中真空抽入溶剂冰乙酸，人工投入中间体Q、间氨基苯甲酸，然后采用循环热水升温至35-40℃保温反应3h；反应结束后，采用循环冷却水降至室温，向中泵入溶剂乙酸乙酯，搅拌2h后离心，湿品送入真空干燥烘箱保持40℃烘干后得尔它培南侧链；该过程间氨基苯甲酸过量，转化率84%；尔它培南侧链的收率为76.14%；冰乙酸、乙酸乙酯作为溶剂使用，离心母液进入溶剂回收系统回收乙酸乙酯和乙酸：先常压下热水加热回收釜温度升高至85℃，回收乙酸乙酯，再减压至-0.098MPa、T=85℃ 回收乙酸。
CN201610469508.5A 2016-06-26 2016-06-26 一种尔它培南侧链生产工艺 Pending CN106565579A (zh)

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Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1079224A (zh) * 1992-02-04 1993-12-08 曾尼卡有限公司 抗菌素化合物
WO1999002531A1 (en) * 1997-07-09 1999-01-21 Merck & Co., Inc. Process for synthesizing carbapenem side chain intermediates
US5872250A (en) * 1997-07-30 1999-02-16 Merck & Co., Inc. Process for synthesizing carbapenem antibiotics
CN1225636A (zh) * 1996-07-12 1999-08-11 麦克公司 碳代青霉烯抗菌剂的合成方法
CN1752074A (zh) * 2005-10-20 2006-03-29 上海交通大学 尔他培南的中间体n－保护－(2s,4s)－2－[(3－羟基羰基)－苯基氨基甲酰基]－吡咯烷－4－基硫醇
CN1752090A (zh) * 2005-10-20 2006-03-29 上海交通大学 尔他培南钠盐的制备方法
CN1800162A (zh) * 2005-10-20 2006-07-12 上海交通大学 N－保护尔他培南中间体的制备方法
CN102264744A (zh) * 2008-12-25 2011-11-30 株式会社钟化 碳青霉烯侧链中间体的改良制造方法
CN104130262A (zh) * 2014-08-12 2014-11-05 湖南凯米尔生物科技有限公司 一种厄他培南、厄他培南侧链及其制备方法
CN105566193A (zh) * 2015-12-18 2016-05-11 邯郸市康瑞生物科技有限公司 一种厄他培南侧链的改良制造方法

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1079224A (zh) * 1992-02-04 1993-12-08 曾尼卡有限公司 抗菌素化合物
CN1225636A (zh) * 1996-07-12 1999-08-11 麦克公司 碳代青霉烯抗菌剂的合成方法
WO1999002531A1 (en) * 1997-07-09 1999-01-21 Merck & Co., Inc. Process for synthesizing carbapenem side chain intermediates
US5872250A (en) * 1997-07-30 1999-02-16 Merck & Co., Inc. Process for synthesizing carbapenem antibiotics
CN1752074A (zh) * 2005-10-20 2006-03-29 上海交通大学 尔他培南的中间体n－保护－(2s,4s)－2－[(3－羟基羰基)－苯基氨基甲酰基]－吡咯烷－4－基硫醇
CN1752090A (zh) * 2005-10-20 2006-03-29 上海交通大学 尔他培南钠盐的制备方法
CN1800162A (zh) * 2005-10-20 2006-07-12 上海交通大学 N－保护尔他培南中间体的制备方法
CN102264744A (zh) * 2008-12-25 2011-11-30 株式会社钟化 碳青霉烯侧链中间体的改良制造方法
CN104130262A (zh) * 2014-08-12 2014-11-05 湖南凯米尔生物科技有限公司 一种厄他培南、厄他培南侧链及其制备方法
CN105566193A (zh) * 2015-12-18 2016-05-11 邯郸市康瑞生物科技有限公司 一种厄他培南侧链的改良制造方法

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* Cited by examiner, † Cited by third party
Title
史颖,等: "厄他培南钠的合成研究", 《中国抗生素杂志》 *

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