Azanium;azane;2,3,4-trihydroxy-4-oxobutanoate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: Azanium;azane;2,3,4-trihydroxy-4-oxobutanoate
• 英文别名: azanium;azane;2,3,4-trihydroxy-4-oxobutanoate
• 化学式: C4H12N2O6
• 分子量: 184.15
• InChiKey: NGPGDYLVALNKEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.04
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  123
• 氢给体数：
  4
• 氢受体数：
  6

ADMET

毒理性

• 毒性总结

识别和使用：酒石酸二铵L-(+)-形成晶体或白色颗粒。它用于纺织工业。它也适用于使用电子自旋共振（ESR）的临床剂量测定。人体研究：在化学烧伤后，使用pH为7的10%溶液在患者眼睛上似乎没有造成明显的额外伤害，但治疗是痛苦的，尤其是如果溶液已经分解并且不再是中性的。动物研究：10%的溶液并不是完全无害的。将pH为7的这种溶液连续施用于兔子眼睛30分钟，在机械去除上皮后没有造成永久性损伤，但确实导致了持续数天的角膜水肿。

IDENTIFICATION AND USE: Diammonium L-(+)-tartrate forms crystals or white granules. It is used in the textile industry. It is also suitable for clinical dosimetry using electron spin resonance (ESR). HUMAN STUDIES: Use of a 10% solution at pH 7 on patients' eyes following chemical burns seems to have caused no recognized additional injury, but the treatment is painful, especially if solution has decomposed and is no longer neutral. ANIMAL STUDIES: A 10% solution is not completely innocuous. Such a solution at pH 7 applied continuously for 30 minutes to a rabbit's eye after mechanical removal of epithelium caused no permanent damage, but did cause edema of the cornea lasting several days.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

立即急救：确保已经进行了充分去污。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、气囊面罩装置或口袋面罩，按训练进行操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者向前倾或将其置于左侧（如果可能，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。/有机酸及相关化合物/

Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Organic acids and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道（如需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有必要，协助呼吸。通过非重复呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的咳嗽反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释。活性炭无效……。不要尝试中和，因为会放热反应。在去污染后，用干燥、无菌敷料覆盖皮肤烧伤……。/有机酸及其相关化合物/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist respirations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Activated charcoal is not effective ... . Do not attempt to neutralize, because of exothermic reaction. Cover skin burns with dry, sterile dressings after decontamination ... . /Organic acids and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于失去意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽插管以控制气道。在上呼吸道阻塞的第一个迹象出现时，可能需要早期插管。使用气囊面罩装置的正压通气技术可能有益。考虑对肺水肿进行药物治疗...。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇...。监测心率和必要时治疗心律失常。开始静脉输注5%葡萄糖水TKO。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液（LR）。对于伴有低血容量迹象的低血压，谨慎给予液体。如果病人在正常血容量下出现低血压，考虑使用血管加压药。注意液体过载的迹象...。使用丙美卡因盐酸协助眼部冲洗...。/有机酸及其相关化合物/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Early intubation, at the first sign of upper airway obstruction, may be necessary. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary. Start IV administration of D5W TKO. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Organic acids and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

如果这种化学物质进入眼睛，请立即移除隐形眼镜，并立即冲洗至少15分钟，不时提起上下眼睑。立即寻求医疗帮助。如果这种化学物质接触到皮肤，请脱掉受污染的衣物，并立即用肥皂和水清洗。立即寻求医疗帮助。如果吸入了这种化学物质，请远离暴露源，如果呼吸停止，开始进行急救呼吸（使用通用防护措施，包括复苏面罩），如果心脏停止，进行心肺复苏。迅速转移到医疗机构。当这种化学物质被吞下时，请寻求医疗帮助。...建议在吸入过量后24-48小时内进行医疗观察，因为肺水肿可能会延迟发生。对于肺水肿的急救，医生或授权的急救人员可能会考虑使用皮质类固醇喷雾。

If this chemical gets into the eyes, remove any contact lenses at once and irrigate immediately for at least 15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts the skin, remove contaminated clothing and wash immediately with soap and water. Seek medical attention immediately. If this chemical has been inhaled, remove from exposure, begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR if heart action has stopped. Transfer promptly to a medical facility. When this chemical has been swallowed, get medical attention. ... Medical observation is recommended for 24-48 hr after breathing overexposure, as pulmonary edema may be delayed. As first aid for pulmonary edema, a doctor or authorized paramedic may consider administering a corticosteroid spray.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-3-(naphthyloxy)-3-(2-thienyl)propylamine D-tartrate 、 酒石酸 、 、 、 Azanium;azane;2,3,4-trihydroxy-4-oxobutanoate 、 、 以by isolating the salt (S)—N,N-dimethyl-3-(naphthyloxy)-3-(2-thienyl)propylamine/D-tartrate (2:1) (Scheme 2)的产率得到(S)-N,N-dimethyl-3-(naphthyloxy)-3-(2-thienyl)propylamine D-tartrate
  参考文献：
  名称：

  Method for the preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine hydrochloride (duloxetine)

  摘要：

  从duloxetine base制备duloxetine hydrochloride盐的方法，包括以下步骤：在乙基甲酮中用浓盐酸反应duloxetine base，然后从乙基甲酮中的浓盐酸中结晶出duloxetine hydrochloride盐。

  公开号：

  US08207356B2
• 作为产物：
  描述：

  (1S,4R)-4-氨基-2-环戊烯-1-羧酸甲酯(2R,3R)-2,3-二羟基丁烷二酸酯 、 氯化铵 、 、 氨 、 甲醇 以 乙醇 为溶剂， 反应 2.0h， 生成 Azanium;azane;2,3,4-trihydroxy-4-oxobutanoate
  参考文献：
  名称：

  Process for preparing (-)-(1S, 4R) N-protected 4-amino-2-cyclopentene-1-carboxylate esters

  摘要：

  本发明涉及一种制备（-）-（1S,4R）N保护的4-氨基-2-环戊烯-1-羧酸酯化合物的方法，其化学式表示为（I）1，其中R1和R2如规范中所述。

  公开号：

  US20020052524A1

文献信息

• Method for the Preparation of (S)-N-Methyl-3-(1-Naphthyloxy)-3-(2-Thienyl)Propylamine Hydrochloride (Duloxetine)
  申请人：Ridvan Ludek

  公开号：US20080293952A1

  公开（公告）日：2008-11-27

  A method of preparation of (S)—N-methyl-3-(1-naphthyloxy)-3-(2-mienyl)propylamine of Formula (I) and its pharmaceutically acceptable salts, comprising a) reaction of (RS)—N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine with optically active D-tartaric acid or an acid salt derived from D-tartaric acid forming a mixture of diastereoisomeric salts of N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine and D-tartaric acid (2:1), b) isolation of the salt (S)—N,N-dimethyl-3-(naphthyloxy)-3-(2-thienyl)propylamine/D-tartrate (2:1) from the mixture of diastereoisomeric salts in an organic solvent, water or a mixture thereof and release of (S)—N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by action of an inorganic or organic base, c) demethylation of (S)—N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by action of an alkylchloroformate of formula ClCOOR (R=C 1 -C 5 alkyl, or C 6 -C 12 aryl or alkylraryl), especially phenyl, ethyl or methyl chloroformate, and d) hydrolytic release of the duloxetine base of formula I and optionally conversion of the base to a salt with the respective acid, or salt of a weak base.

  一种制备（S）-N-甲基-3-（1-萘氧基）-3-（2-米芥基）丙胺（I式）及其药学上可接受的盐的方法，包括a）将（RS）-N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺与光学活性D-酒石酸或由D-酒石酸衍生的酸盐反应，形成N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺和D-酒石酸的两对映异构盐的混合物（2：1），b）在有机溶剂、水或其混合物中从映异构盐混合物中分离出（S）-N，N-二甲基-3-（萘氧基）-3-（2-噻吩基）丙胺/D-酒石酸盐（2：1），并通过一种无机或有机碱的作用释放（S）-N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺，c）通过一种公式为ClCOOR（R = C1-C5烷基或C6-C12芳基或烷基芳基）的烷基氯甲酸酯（特别是苯基、乙基或甲基氯甲酸酯）的作用脱甲基化（S）-N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺，d）水解释放出公式I的度洛西汀基，可选地将该基转化为相应酸的盐或弱碱盐。
• Method for the preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine hydrochloride (duloxetine)
  申请人：Zentiva k.s.

  公开号：US08071791B2

  公开（公告）日：2011-12-06

  A method of preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-mienyl)propylamine of Formula (I) and its pharmaceutically acceptable salts, comprising a) reaction of (RS)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine with optically active D-tartaric acid or an acid salt derived from D-tartaric acid forming a mixture of diastereoisomeric salts of N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine and D-tartaric acid (2:1), b) isolation of the salt (S)-N,N-dimethyl-3-(naphthyloxy) -3-(2-thienyl)propylamine/D-tartrate (2:1) from the mixture of diastereoisomeric salts in an organic solvent, water or a mixture thereof and release of (S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by action of an inorganic or organic base, c) demethylation of (S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by action of an alkylchloroformate of formula ClCOOR (R=C1-C5 alkyl, or C6-C12 aryl or alkylraryl), especially phenyl, ethyl or methyl chloroformate, and d) hydrolytic release of the duloxetine base of formula I and optionally conversion of the base to a salt with the respective acid, or salt of a weak base.

  一种制备（S）-N-甲基-3-（1-萘氧基）-3-（2-米尼尔基）丙胺的方法，其化学式为（I），以及其药学上可接受的盐，包括a）将（RS）-N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺与光学活性的D-酒石酸或由D-酒石酸衍生的酸盐反应，形成N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺和D-酒石酸（2：1）的非对映异构盐混合物，b）在有机溶剂、水或其混合物中分离出（S）-N，N-二甲基-3-（萘氧基）-3-（2-噻吩基）丙胺/D-酒石酸盐（2：1）的盐，通过一个无机或有机碱作用释放（S）-N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺，c）通过一个化学式为ClCOOR（R=C1-C5烷基或C6-C12芳基或烷基芳基）的烷基氯甲酸酯，特别是苯基、乙基或甲基氯甲酸酯，作用于（S）-N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺，去甲基化，d）水解释放出化学式I的度洛西汀基，并可选择将其转化为相应酸的盐或弱碱盐。
• Process for preparing (-)-(1S, 4R) N-protected 4-amino-2-cyclopentene-1-carboxylate esters
  申请人：——

  公开号：US20020052524A1

  公开（公告）日：2002-05-02

  The invention relates to a process for preparing (−)-(1S,4R) N protected 4-amino-2-cylcopentene-1-carboxylate esters represented by the formula (I) 1 wherein R 1 and R 2 are as described within the specification.

  本发明涉及一种制备（-）-（1S,4R）N保护的4-氨基-2-环戊烯-1-羧酸酯化合物的方法，其化学式表示为（I）1，其中R1和R2如规范中所述。
• METHOD FOR THE PREPARATION OF (S)-N-METHYL-3-(1-NAPHTHYLOXY)-3-(2-THIENYL)PROPYLAMINE HYDROCHLORIDE (DULOXETINE)
  申请人：RIDVAN Ludek

  公开号：US20120029212A1

  公开（公告）日：2012-02-02

  A method for the preparation of a duloxetine hydrochloride salt from a duloxetine base, comprising the steps of: reacting duloxetine base with concentrated hydrochloric acid in ethylmethylketone; and crystallizing duloxetine hydrochloride salt from said concentrated hydrochloric acid in ethylmethylketone.

  一种从多鲁替林碱制备多鲁替林盐酸盐的方法，包括以下步骤：在乙基甲酮中，用浓盐酸与多鲁替林碱反应；并从浓盐酸中在乙基甲酮中结晶多鲁替林盐酸盐。