甲基物 | 35511-15-0

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 中文名称: 甲基物
• 中文别名: 吡罗昔康杂质J；2-甲基-4-羟基-2H-1,2-苯并异噻嗪-3-羧酸甲酯-1,1-二氧化物；吡罗昔康甲基物；2-溴苯甲酸甲酯；4-羟基-2-甲基-2H-1,2-苯并噻嗪-3-羧酸甲酯-1,1-二氧化物；2-甲基-4-羟基-2H-1,2-苯并噻唑-3-羧酸甲酯-1,1-二氧化物；甲基4-羟基-2-甲基-2H-1,2-苯并噻嗪-3-羧酸盐1,1-二氧化物；2-甲基-4-羟基-2H-1,2-苯并噻唑-3-羟酸甲酯-1,1-二氧化物；2-甲基-4-羟基-2H-1,2-苯并异噻嗪-3-羧酸乙酯-1,1-二氧化物
• 英文名称: methyl 2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide
• 英文别名: methyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide；4-hydroxy-3-carbomethoxy-2-methyl-2H-1,2-benzothiazine 1,1-dioxide；2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylic acid methyl ester 1,1-dioxide；methyl 4-hydroxy-2-methyl-1,1-dioxo-1λ6,2-benzothiazine-3-carboxylate
• CAS: 35511-15-0
• 化学式: C₁₁H₁₁NO₅S
• mdl: MFCD00071766
• 分子量: 269.278
• InChiKey: NGHIOTWSWSQQNT-UHFFFAOYSA-N

物化性质

• 熔点：
  163-165°C
• 沸点：
  439.9±55.0 °C(Predicted)
• 密度：
  1.514±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  92.3
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2934991000
• WGK Germany：
  3
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  -20°C 冰箱

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 2-Methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylic methyl ester-1,1-dioxide
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 2-Methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylic methyl ester-1,1-dioxide
CAS number: 35511-15-0

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C11H11NO5S
Molecular weight: 269.3

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, sulfur oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途：它是合成炎痛喜康等镇痛药物的中间体。

反应信息

• 作为反应物：
  描述：

  甲基物 在 磷酸 、 一水合肼 作用下， 以 甲醇 为溶剂， 反应 0.84h， 生成 4-hydroxy-N'-[(1E)-1-(3-hydroxyphenyl)ethylidene]-2-methyl-2H-1,2-benzothiazine-3-carbohydrazide 1,1-dioxide
  参考文献：
  名称：

  微波辅助合成4-羟基-N '-[1-苯乙叉基] -2 H / 2-甲基-1,2-苯并噻嗪-3-碳酰肼1,1-二氧化物作为抗菌剂

  摘要：

  由市售糖精钠合成了一系列的4-羟基-N '-[1-苯乙叉基] -2 H / 2-甲基，1,2-苯并噻嗪-3-碳酰肼1,1-二氧化物。（1,1-dioxido-3-oxo-1,2，benzisothiazol-2（3 H）-yl）acetate的碱催化的环扩环反应，然后进行超声波介导的肼解反应，随后在微波的影响下与1-苯基乙酮反应生成标题化合物。此外，微波辅助合成1,4-二氢吡唑并[4,3- c ] [1,2]苯并噻嗪-3-醇5,5-二氧化物和4-甲基-1,4-二氢吡唑并[4,3- c还讨论了] [1,2]苯并噻嗪-3-醇5,5-二氧化物。发现大多数合成的化合物具有中等至重要的抗微生物（抗细菌和抗真菌）活性。发现具有更大亲脂性的化合物（N-甲基类似物）具有更高的抗菌活性。

  DOI：

  10.1016/j.ejmech.2011.03.020
• 作为产物：
  描述：

  糖精 在 sodium methylate 、 sodium hydride 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 13.0h， 生成 甲基物
  参考文献：
  名称：

  通过钌（II）催化的动态动力学拆分-不对称转移加氢立体异构官能化的苯甲磺胺

  摘要：

  高度非对映和对映选择性的Ru（II）催化的动态动力学拆分-α-（N-磺酰氨基）和α-（N-磺酰氨基）芳基酮的不对称转移氢化（DKR-ATH）生成4-羟基-苯并-δ -和3-（α-羟基-芳基甲基）-苯并-γ-sultams被提出。通过采用对映体纯的柄-Ru [PipSO 2 DPEN（CH 2）4 PH]猫。在HCO 2 H / Et 3 N二元混合物中S / C = 10000的II，在温和条件下以100％的转化率可获得高达> 99.9％ee和dr> 99：1的dr。申请访问立体纯“结构简化的TsDPEN” N，N-配体s yn-3-（α氨基苄基） -苯并-γ-磺内酰胺（“ SYN -ULTAM”）及其结构异构体的反式-4-氨基-3-苯基-苯并-δ-磺内酰胺（反式- 4）是证明。

  DOI：

  10.1021/acs.orglett.7b00670

文献信息

• Process for the preparation of
  申请人：Warner-Lambert Company

  公开号：US03960856A1

  公开（公告）日：1976-06-01

  An improved process for the preparation of 4-hydroxy-3-(5-methyl-3-isoxazolylcarbamoyl)-2-methyl-2H-1,2-benzothiazine 1,1-dioxide (I), a known anti-inflammatory agent, requires the use of specific proportions of reactants and carefully controlled reaction conditions. An alkali metal alkoxide, suspended in dimethylformamide is combined, with stirring, as rapidly as possible with a solution of alkyl 2,3-dihydro-3-oxo-1,2-benzisothiazole-2-acetate 1,1-dioxide (II) in dimethylformamide, while maining the internal reaction temperature within 15.degree.-30.degree.C. More than two but less than six moles of the alkoxide are used per mole of the alkyl 2,3-dihydro-3-oxo-1,2-benzisothiazole-2-acetate 1,1-dioxide (II). After all reactants have been combined, stirring is continued for a specific period of time and then the reaction mixture is acidified. Total elapsed time from initial combination of reactants to acidification is from 30 to 50 minutes. Acidification of the reaction mixture precipitates out alkyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (III) in substantially pure form in high yields, without recrystallization. Product III is methylated on the sulfonamide nitrogen and reacted with 3-amino-5-methyl-isoxazole to obtain crude I. A further improvement in the process of the invention involves a more efficient method for purifying crude product I: the need for large quantities of dioxane solvent is obviated. After slurrying and washing, product I is solubilized in dilute alkali, and decolorized. After filtration and acidification pure product I in high yield is obtained. In addition to preparing the known anti-inflammatory agent (I), the initial reaction step of the invention wherein 2,3-dihydro-3-oxo-1,2-benzisothiazole-2-acetate, 1,1-dioxide (II) is rearranged to form alkyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (III), may be used with particular advantage for the preparation of other useful benzothiazine derivatives.

  一种改进的制备4-羟基-3-(5-甲基-3-异噁唑基甲酰基)-2-甲基-2H-1,2-苯并噻嗪-1,1-二氧化物（I），一种已知的抗炎药物的过程，需要使用特定比例的反应物和精确控制的反应条件。在二甲基甲酰胺中悬浮的碱金属烷氧化物与二甲基甲酰胺中的烷基2,3-二氢-3-酮-1,2-苯并噻嗪-2-乙酸酯1,1-二氧化物（II）的溶液迅速混合，并在保持内部反应温度在15度至30度之间的情况下搅拌。每摩尔烷氧化物使用两个以上但少于六个摩尔的烷基2,3-二氢-3-酮-1,2-苯并噻嗪-2-乙酸酯1,1-二氧化物（II）。在所有反应物混合后，继续搅拌一段特定时间，然后将反应混合物酸化。从初始混合反应物到酸化的总经过时间为30至50分钟。酸化反应混合物使烷基4-羟基-2H-1,2-苯并噻嗪-3-羧酸酯1,1-二氧化物（III）以高收率的基本纯形式沉淀出来，无需再结晶。产品III在磺胺酰氮上甲基化，并与3-氨基-5-甲基-异噁唑发生反应，得到粗I。发明的过程中的进一步改进涉及一种更有效的精制粗产品I的方法：无需大量二噁烷溶剂。在搅拌和洗涤后，产品I在稀碱中溶解，并脱色。经过过滤和酸化后，高收率得到纯产品I。除了制备已知的抗炎药物（I）外，发明的初始反应步骤中，其中2,3-二氢-3-酮-1,2-苯并噻嗪-2-乙酸酯，1,1-二氧化物（II）被重新排列以形成烷基4-羟基-2H-1,2-苯并噻嗪-3-羧酸酯1,1-二氧化物（III），可能特别有利于制备其他有用的苯并噻嗪衍生物。
• Benzothiazine dioxides as endothelin antagonists
  申请人：Warner-Lambert Company

  公开号：US05599811A1

  公开（公告）日：1997-02-04

  Novel benzothiazine dioxides which are antagonists of endothelin are described, as well as novel intermediates used in their preparation, methods for the preparation, and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, essential renovascular malignant and pulmonary hypertension, cerebral infarction, cerebral ischemia, congestive heart failure, and subarachnoid hemorrhage.

  描述了一种新型苯并噻嗪二氧化物，它们是内皮素拮抗剂，以及用于它们制备的新型中间体，制备方法，以及相同的药物组合物，这些药物组合物在治疗内皮素水平升高、肾血管性恶性高血压和肺动脉高压、脑梗死、脑缺血、充血性心力衰竭和蛛网膜下腔出血方面是有用的。
• Synthesis, monoamine oxidase inhibition activity and molecular docking studies of novel 4-hydroxy-N′-[benzylidene or 1-phenylethylidene]-2-H/methyl/benzyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides
  作者：Furqan Ahmad Saddique、Sumera Zaib、Saquib Jalil、Sana Aslam、Matloob Ahmad、Sadia Sultan、Humera Naz、Mazhar Iqbal、Jamshed Iqbal

  DOI：10.1016/j.ejmech.2017.10.036

  日期：2018.1

  Three series of 4-hydroxy-N′-[benzylidene/1-phenylethylidene]-2-H/methyl/benzyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides (9–11)a-l were synthesized and unraveled to be highly potent dual inhibitors of monoamine oxidases (MAO-A and MAO-B). All the examined compounds demonstrated IC50 values in lower micro-molar range for both MAO-A as well as MAO-B. The most active MAO-A inhibitor was 4-hydr

  合成并解开了三个系列的4-羟基-N ' -[亚苄基/ 1-苯亚乙基] -2- H /甲基/苄基-1,2-苯并噻嗪-3-碳酰肼1,1-二氧化物（9-11）al是高效的单胺氧化酶双重抑制剂（MAO-A和MAO-B）。对于MAO-A和MAO-B，所有检查的化合物均在较低的微摩尔范围内显示出IC 50值。最具活性的MAO-A抑制剂是4-羟基-N' -（1-苯基亚乙基）-2 H-苯并[ e ] [1,2]噻嗪-3-碳酰肼1,1-二氧化物（9i），IC 50值为0.11±0.005μM，而甲基4-羟基-2 H-苯并[e ] [1,2]噻嗪-3-羧酸盐1,1-二氧化物（3）是最具活性的MAO-B抑制剂，IC 50值为0.21±0.01μM。酶动力学研究表明，最有效的化合物以竞争性方式抑制两种MAO酶（A和B）。还进行了分子对接研究，以直观了解有效抑制剂的潜在抑制作用。这些化合物的高功效可与预期的良好口服
• 1,2-Benzothiazine 1,1-Dioxide P₂−P₃ Peptide Mimetic Aldehyde Calpain I Inhibitors
  作者：Gregory J. Wells、Ming Tao、Kurt A. Josef、Ron Bihovsky

  DOI：10.1021/jm010178b

  日期：2001.10.1

  A series of peptide mimetic aldehyde inhibitors of calpain I was prepared in which the P(2) and P(3) amino acids were replaced by substituted 3,4-dihydro-1,2-benzothiazine-3-carboxylate 1,1-dioxides. The effect of 2, 6, and 7-benzothiazine substituents and the P(1) amino acid was examined. Potency of these inhibitors, 15c-p, against human recombinant calpain I is particularly dependent upon the 2-substituent

  制备了一系列钙蛋白酶I的肽模拟醛抑制剂，其中P（2）和P（3）氨基酸被取代的3,4-二氢-1,2-苯并噻嗪-3-羧酸1,1-二氧化物取代。检查了2、6和7-苯并噻嗪取代基和P（1）氨基酸的作用。这些抑制剂15c-p对人重组钙蛋白酶I的效力特别取决于2-取代基，其中甲基和乙基通常比氢，异丙基，异丁基或苄基更有效。15m的更有效的非对映异构体在3,4-二氢-1,2-苯并噻嗪的3位上具有（S）绝对构型。该系列中最佳抑制剂的效能（IC（50）= 5-7 nM）与在P（2）处带有L-Leu或L-Val残基的常规N-苄氧基羰基二肽醛抑制剂的性能相比具有优势。
• 4-Hydroxy-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxides and salts
  申请人：Boehringer Ingelheim GmbH

  公开号：US04233299A1

  公开（公告）日：1980-11-11

  Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, methyl or ethyl; R.sub.2 is methyl, ethyl or n-propyl; and Y is hydrogen, methyl, methoxy, fluorine or chlorine; and non-toxic, pharmacologically acceptable salts thereof formed with an inorganic or organic base. The compounds as well as their salts are useful as antiphlogistics.

  式##STR1##中的化合物，其中R.sub.1为氢、甲基或乙基；R.sub.2为甲基、乙基或正丙基；Y为氢、甲基、甲氧基、氟或氯；以及与无机或有机碱形成的非毒性、药理学上可接受的盐。这些化合物及其盐可用作抗炎药。