CN103923014A - 环肌酸制备方法 - Google Patents

环肌酸制备方法 Download PDF

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Publication number
CN103923014A
CN103923014A CN201410185623.0A CN201410185623A CN103923014A CN 103923014 A CN103923014 A CN 103923014A CN 201410185623 A CN201410185623 A CN 201410185623A CN 103923014 A CN103923014 A CN 103923014A
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Prior art keywords
ethylenediamine
preparation
quadrol
sodium
acetonitrile
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CN201410185623.0A
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English (en)
Inventor
马杰
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NINGXIA BAOMA PHARMACEUTICAL Co Ltd
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NINGXIA BAOMA PHARMACEUTICAL Co Ltd
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Application filed by NINGXIA BAOMA PHARMACEUTICAL Co Ltd filed Critical NINGXIA BAOMA PHARMACEUTICAL Co Ltd
Priority to CN201410185623.0A priority Critical patent/CN103923014A/zh
Publication of CN103923014A publication Critical patent/CN103923014A/zh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D233/44—Nitrogen atoms not forming part of a nitro radical
    • C07D233/46—Nitrogen atoms not forming part of a nitro radical with only hydrogen atoms attached to said nitrogen atoms

Abstract

一种环肌酸制备方法，以乙二胺和羟基乙腈为原料在0~20℃反应缩合得到乙二胺基乙腈，然后将乙二胺基乙腈在60~100℃下与氢氧化钠催化水解得乙二胺基乙酸钠，再将乙二胺基乙酸钠在甲醇溶液环境下经溴化腈加成环合得环肌酸。本发明合成路径短，副产品均可回收利用，没有固体、气体残渣污物，工艺上产生的氨气用水吸收作为氨水出售，成品母液形成的溴化钠，通过减压浓缩得到固体溴化钠，可以作为无机化工原料出售。

Description

环肌酸制备方法
技术领域：
本发明涉及一种环肌酸制备方法。
背景技术：
环肌酸化学名称为2-亚氨基-1-咪唑烷乙酸，结构式为：
环肌酸的应用目前文献报道极少，就目前已知内容它是人体非必需的氨基酸，是含有咪唑杂环的氨基酸，其作为运动营养品为人们所知，同时，有报道其有抗癌作用。环肌酸价格昂贵，目前尚未发现生产厂家，并且其合成方法及合成条件的文献报道未见公开。
发明内容：
鉴于此，有必要找到一种环肌酸制备方法。
一种环肌酸制备方法，以乙二胺和羟基乙腈为原料在0~20℃反应缩合得到乙二胺基乙腈：
,（1）
然后将乙二胺基乙腈在60~100℃下与氢氧化钠催化水解得乙二胺基乙酸钠： 
， （2）
再将乙二胺基乙酸钠在甲醇溶液环境下经溴化腈加成环合得环肌酸：
，              （3）
优选的，式（1）的反应温度为20℃，式（2）的反应温度为100℃。
本发明合成路径短，副产品均可回收利用，没有固体、气体残渣污物，工艺上产生的氨气用水吸收作为氨水出售，成品母液形成的溴化钠，通过减压浓缩得到固体溴化钠，可以作为无机化工原料出售。此工艺无论从环保还是成本上都起到了积极作用。
具体实施方式：
    一种环肌酸制备方法，以乙二胺和羟基乙腈为原料在0~20℃反应缩合得到乙二胺基乙腈：
，（1）
然后将乙二胺基乙腈在60~100℃下与氢氧化钠催化水解得乙二胺基乙酸钠： 
，   （2）
再将乙二胺基乙酸钠在甲醇溶液环境下经溴化腈加成环合得环肌酸：
，              （3）
在本实施方式中，式（1）的反应温度为20℃，式（2）的反应温度为100℃。

Claims (2)

1.一种环肌酸制备方法，其特征在于：以乙二胺和羟基乙腈为原料在0~20℃反应缩合得到乙二胺基乙腈：
，（1）
然后将乙二胺基乙腈在60~100℃下与氢氧化钠催化水解得乙二胺基乙酸钠： 
，                                                       （2）
再将乙二胺基乙酸钠在甲醇溶液环境下经溴化腈加成环合得环肌酸：
，              （3）。
2.如权利要求1所述的环肌酸制备方法，其特征在于：式（1）的反应温度为20℃，式（2）的反应温度为100℃。
CN201410185623.0A 2014-05-05 2014-05-05 环肌酸制备方法 Pending CN103923014A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410185623.0A CN103923014A (zh) 2014-05-05 2014-05-05 环肌酸制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410185623.0A CN103923014A (zh) 2014-05-05 2014-05-05 环肌酸制备方法

Publications (1)

Publication Number Publication Date
CN103923014A true CN103923014A (zh) 2014-07-16

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016036699A1 (en) * 2014-09-03 2016-03-10 Lumos Pharma, Inc. Synthesis of cyclocreatine and analogs thereof
JP2018513122A (ja) * 2015-03-11 2018-05-24 ルモス ファーマ， インコーポレイテッド シクロクレアチンおよびその類似体の合成

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1439005A (zh) * 2000-02-15 2003-08-27 苏根公司 吡咯取代的2－二氢吲哚酮蛋白激酶抑制剂
CN1541098A (zh) * 2001-08-15 2004-10-27 �ո��� 用于癌症治疗的联合疗法
WO2006073923A2 (en) * 2004-12-30 2006-07-13 Nour Heart, Inc. Phosphagen synthesis

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1439005A (zh) * 2000-02-15 2003-08-27 苏根公司 吡咯取代的2－二氢吲哚酮蛋白激酶抑制剂
CN1541098A (zh) * 2001-08-15 2004-10-27 �ո��� 用于癌症治疗的联合疗法
WO2006073923A2 (en) * 2004-12-30 2006-07-13 Nour Heart, Inc. Phosphagen synthesis

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ROWLEY G. L.等: "On the Specificity of Creatine Kinase. New Glycocyamines and Glycocyamine Analogs Related to Creatine", 《J. AM. CHEM. SOC.》 *
姚方等: "肌氨酸钠的合成研究", 《科技进展》 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016036699A1 (en) * 2014-09-03 2016-03-10 Lumos Pharma, Inc. Synthesis of cyclocreatine and analogs thereof
CN107001280A (zh) * 2014-09-03 2017-08-01 卢莫斯制药公司 环肌酸及其类似物的合成
AU2015312159B2 (en) * 2014-09-03 2019-03-07 Lumos Pharma, Inc. Synthesis of cyclocreatine and analogs thereof
US10493062B2 (en) 2014-09-03 2019-12-03 Lumos Pharma, Inc. Synthesis of cyclocreatine and analogs thereof
JP2018513122A (ja) * 2015-03-11 2018-05-24 ルモス ファーマ， インコーポレイテッド シクロクレアチンおよびその類似体の合成
US10081605B2 (en) 2015-03-11 2018-09-25 Lumos Pharma, Inc. Synthesis of cyclocreatine and analogs thereof
US10377721B2 (en) 2015-03-11 2019-08-13 Lumos Pharma, Inc. Synthesis of cyclocreatine and analogs thereof

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Application publication date: 20140716