1,2,3,9-四氢-9-甲基-3-亚甲咔唑酮 | 99614-64-9

• 物质功能分类: 分析化学 - 分析试剂 - 离子色谱试剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 1,2,3,9-四氢-9-甲基-3-亚甲咔唑酮
• 中文别名: 1,2,3,9-四氢-9甲基-3-亚甲咔唑酮
• 英文名称: 9-methyl-3-methylene-1,2,3,9-tetrahydro-4H-carbazol-4-one
• 英文别名: 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one；9-methyl-3-methylene-1,2,3,9-tetradydro-4H-carbazol-4-one；9-methyl-3-methylidene-1,2-dihydrocarbazol-4-one
• CAS: 99614-64-9
• 化学式: C₁₄H₁₃NO
• 分子量: 211.263
• InChiKey: AGQJDIDJKSFVTC-UHFFFAOYSA-N

物化性质

• 沸点：
  394℃
• 密度：
  1.18
• 闪点：
  192℃
• 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)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险品标志：
  T
• 安全说明：
  S36/37,S45
• 危险类别码：
  R25,R43
• WGK Germany：
  3
• 海关编码：
  2933990090
• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P280
• 危险品运输编号：
  2811
• 危险性描述：
  H301,H317
• 储存条件：
  | 2-8°C |

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : 9-Methyl-3-methylene-1,2,3,9-tetrahydro-4H-
carbazol-4-one
CAS-No. : 99614-64-9
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP]
Acute toxicity, Oral (Category 3)
Skin sensitization (Category 1)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Toxic if swallowed. May cause sensitization by skin contact.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Danger
Hazard statement(s)
H301 Toxic if swallowed.
H317 May cause an allergic skin reaction.
Precautionary statement(s)
P280 Wear protective gloves.
P301 + P310 IF SWALLOWED: Immediately call a POISON CENTER or doctor/
physician.
Supplemental Hazard none
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R25 Toxic if swallowed.
R43 May cause sensitization by skin contact.
S-phrase(s)
S36/37 Wear suitable protective clothing and gloves.
S45 In case of accident or if you feel unwell, seek medical advice immediately
(show the label where possible).
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Formula : C14H13NO
Molecular Weight : 211,26 g/mol
Component Concentration
9-Methyl-3-methylene-1,2,3,9-tetrahydro-4H-carbazol-4-one
CAS-No. 99614-64-9 -

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Section 4. FIRST AID MEASURES
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Take victim immediately to hospital. Consult a physician.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly
investigated.
Indication of any immediate medical attention and special treatment needed
no data available

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Section 5. FIREFIGHTING MEASURES
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx)
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate
ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
Environmental precautions
Prevent further leakage or spillage if safe to do so. Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: 2 - 8 °C
Specific end uses
no data available

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Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the
product.
Personal protective equipment
Eye/face protection
Face shield and safety glasses Use equipment for eye protection tested and approved under
appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the
standard EN 374 derived from it.
Body Protection
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Where risk assessment shows air-purifying respirators are appropriate use a full-face particle
respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering
controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use
respirators and components tested and approved under appropriate government standards such as
NIOSH (US) or CEN (EU).

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and no data available
boiling range
g) Flash point no data available
h) Evaporation rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- log Pow: 3,4
octanol/water
p) Autoignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

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Section 10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available

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Section 11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
no data available
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
May cause allergic skin reaction.
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion Toxic if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes May cause eye irritation.
Signs and Symptoms of Exposure
To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly
investigated.
Additional Information
RTECS: Not available

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Section 12. ECOLOGICAL INFORMATION
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
no data available
Other adverse effects
no data available

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Section 13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

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Section 14. TRANSPORT INFORMATION
UN number
ADR/RID: 2811 IMDG: 2811 IATA: 2811
UN proper shipping name
ADR/RID: TOXIC SOLID, ORGANIC, N.O.S. (Ondansetron hydrochloride dihydrate)
IMDG: TOXIC SOLID, ORGANIC, N.O.S. (Ondansetron hydrochloride dihydrate)
IATA: Toxic solid, organic, n.o.s. (Ondansetron hydrochloride dihydrate)
Transport hazard class(es)
ADR/RID: 6.1 IMDG: 6.1 IATA: 6.1
Packaging group
ADR/RID: III IMDG: III IATA: III
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

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Section 15. REGULATORY INFORMATION
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
no data available
Chemical Safety Assessment
no data available

---

Section 16. OTHER INFORMATION
Further information
Copyright 2011 Co. License granted to make unlimited paper copies for internal use only.
The above information is believed to be correct but does not purport to be all inclusive and shall be used
only as a guide. The information in this document is based on the present state of our knowledge and is
applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Co., shall not be held liable for any damage
resulting from handling or from contact with the above product. See reverse side of invoice or packing slip
for additional terms and conditions of sale.

制备方法与用途

用途
1,2,3,9-四氢-9甲基-3-亚甲咔唑酮是昂丹司琼的一种杂质。昂丹司琼、格拉司琼和多拉司琼是临床上常用的三种止吐药物，其中昂丹司琼是一种有效的、选择性和可逆性的5-羟色胺（5-HT3）受体阻滞剂。它对α1、α2、β1、β2肾上腺素能受体及组胺H1、H2受体的作用极小，并且不拮抗中枢和末梢的多巴胺能受体，能够有效抑制化疗和放射治疗引起的恶心与呕吐。

反应信息

• 作为反应物：
  描述：

  N-(trimethylsilyl)-2-methylimidazole 、 1,2,3,9-四氢-9-甲基-3-亚甲咔唑酮 在 四丁基氟化铵 作用下， 以 乙酸乙酯 为溶剂， 反应 2.17h， 以96.7%的产率得到昂丹司琼
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARING 1,2,3,9-TETRAHYDRO-9-METHYL-3-[(2-METHYL-1H-IMIDAZOLE-1-YL)METHYL]-4H-CARBAZOL-4-ONE OR ITS SALT
  [FR] PROCEDE DE PREPARATION DE 1,2,3,9-TETRAHYDRO-9-METHYL-3-[(2-METHYL-1H-IMIDAZOLE-1-YL)METHYL]-4H-CARBAZOL-4-ONE OU D'UN SEL DE CELUI-CI

  摘要：

  本发明提供了一种改进的制备1,2,3,9-四氢-9-甲基-3-[(2-甲基-1H-咪唑-1-基)甲基]-4H-咔唑-4-酮或其盐的方法，该方法在温和条件下高产率地制备，可作为一种抗呕吐剂使用，并有利于其大规模生产。

  公开号：

  WO2005037823A1
• 作为产物：
  描述：

  昂丹司琼 在 双氧水 、 manganese(ll) chloride 作用下， 以 水 为溶剂， 反应 6.0h， 以47.2%的产率得到1,2,3,9-四氢-9-甲基-3-亚甲咔唑酮
  参考文献：
  名称：

  一种昂丹司琼杂质A的制备方法

  摘要：

  本发明公开了一种昂丹司琼杂质A的制备方法，包括如下步骤：先称取昂丹司琼原料和适量氯化铝，加过氧化氢水溶液溶解制成昂丹司琼溶液，过氧化氢水溶液中过氧化氢的质量分数为12％；将该溶液转移至带有聚四氟乙烯内衬的反应釜，密封后放入烘箱中在140℃反应8h；反应完成，冷却到室温后，乙酸乙酯萃取，收集乙酸乙酯部分，浓缩干燥得到水热反应萃取物；再用HSCCC法对水热反应萃取物进行分离纯化得到杂质A。本发明提供的方法先通过水热反应使得昂丹司琼降解得到杂质A、D，以水为介质，经济环保；再通过HSCCC一步即可分别分离纯化得到杂质A、D，纯度在98％以上。

  公开号：

  CN109020871A
• 作为试剂：
  描述：

  、 昂丹司琼 、 1,2,3,4-四氢-9-甲基-4H-咔唑酮 、 聚合甲醛 、 吗啉 在 1,2,3,9-四氢-9-甲基-3-亚甲咔唑酮 作用下， 以 溶剂黄146 为溶剂， 以to provide 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one (compound of formula 2, Scheme 1)的产率得到1,2,3,9-四氢-9-甲基-3-亚甲咔唑酮
  参考文献：
  名称：

  Process for preparing 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one and ondansetron therefrom

  摘要：

  本发明提供了一种快速高产的制备1,2,3,9-四氢-9-甲基-3-亚甲基-4H-咔唑-4-酮的方法，该方法不使用二级胺作为催化剂，也不使用冰乙酸作为溶剂。本发明还提供了一种快速高产的制备昂丹司琼的方法，该方法不使用氧化铝作为催化剂，而是使用1,2,3,9-四氢-9-甲基-3-亚甲基-4H-咔唑-4-酮作为原料。

  公开号：

  US07696356B2

文献信息

• Process for the preparation of 1,2,3,9-tetrahydro-9-methyl-3-((2-methyl-1H-imidazol-1-yl)-methyl)-4H-carbazol-4-one
  申请人：Hanmi Pharm. Co., Ltd.

  公开号：EP1207160A1

  公开（公告）日：2002-05-22

  Pure 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one or a pharmaceutically acceptable salt thereof is prepared in a high yield by a simple process which reacts 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one with a 2-methylimidazole derivative in an organic solvent or in a mixture of an organic solvent and water in the presence of a halosilane compound.

  通过在有机溶剂或有机溶剂和水的混合物中，在卤代硅烷化合物存在下，将1,2,3,9-四氢-9-甲基-3-[(2-甲基-1H-咪唑-1-基)甲基]-4H-咔唑-4-酮或其药学上可接受的盐与2-甲基咪唑衍生物反应，可以高产率地制备出来。
• Process for the preparation of 1,2,3,9-tetrahydro-9-methyl-3-{(2-methyl-1H-imidazol-1-yl)methyl}-4H-carbazol-4-one
  申请人：Hanmi Pharm. Co., Ltd.

  公开号：US06388091B1

  公开（公告）日：2002-05-14

  Pure -1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one or a pharmaceutically acceptable salt thereof is prepared in a high yield by a simple process which reacts 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one with a 2-methylimidazole derivative in an organic solvent or in a mixture of an organic solvent and water in the presence of a halosilane compound.

  通过在有机溶剂或有机溶剂和水混合物中，在卤代硅烷化合物存在下，将1,2,3,9-四氢-9-甲基-3-[(2-甲基-1H-咪唑-1-基)甲基]-4H-咔唑-4-酮与2-甲基咪唑衍生物反应，可以高产率地制备纯度高的1,2,3,9-四氢-9-甲基-3-[(2-甲基-1H-咪唑-1-基)甲基]-4H-咔唑-4-酮或其药用盐。
• C(sp2)–H Bond Multiple Functionalization in Air for Construction of Tetrahydrocarbazoles with Continuous Quaternary Carbons and Polycyclic Diversification
  作者：Longlong Song、Dan Ni、Shikun Jia、Rou Pi、Suzhen Dong、Fan Yang、Jie Tang、Shunying Liu

  DOI：10.1021/acs.orglett.0c00145

  日期：2020.3.6

  The C(sp2)-H function of indole ketone with diazo compound via a rhodium(II)-catalyzed intramolecular electrophilic trapping reaction under mild conditions in air was demonstrated. The established methodology provided a highly efficient approach for direct synthesis of mutisubstituted tetrahydrocarbazoles with continuous quaternary carbons. The resulting products facilitate further modification to

  在空气中温和条件下，通过铑（II）催化的分子内亲电捕集反应，证实了吲哚酮与重氮化合物的C（sp2）-H功能。建立的方法为直接合成具有连续季碳原子的多取代四氢咔唑提供了一种高效方法。所得产物便于进一步修饰以方便地构建具有另外的稠合杂环的四氢咔唑。通过表型筛选，几种产品在骨肉瘤细胞系中表现出良好的抗癌生物活性。
• [EN] PROCESS FOR MAKING ONDANSETRON AND INTERMEDIATES THEREOF<br/>[FR] PROCEDE DE FABRICATION D'ONDANSETRON ET DE LEURS INTERMEDIAIRES
  申请人：SYNTHON BV

  公开号：WO2004065381A1

  公开（公告）日：2004-08-05

  The invention relates to a process for producing a compound of formula (I), wherein a carbazolone of formula II, formaldehyde or a formaldehyde precursor, an amine of formula III or a salt thereof wherein R1 and R2 each independently represent a C1 to C4 alkyl group or together with the nitrogen atom they form a 5- or 6-membered ring, and an imidazole of formula V or a salt thereof are reacted at elevated temperature in anon-aqueous polar solvent and in the presence of a water binding agent to form the compound of formula (I).

  该发明涉及一种制备化合物的过程，其化学式为(I)，其中在无水极性溶剂中，在高温下，通过在存在水结合剂的情况下，将化学式II的氧代吲哚酮、甲醛或甲醛前体、化学式III的胺或其盐（其中R1和R2各自独立地代表C1到C4烷基或与氮原子一起形成5-或6-成员环）以及化学式V的咪唑或其盐进行反应，以形成化合物的化学式(I)。
• [EN] PROCESS FOR PREPARING 1,2,3,9-TETRAHYDRO-9-METHYL-3-[(2-METHYL-1H-IMIDAZOL-1-YL)METHYL]-4H-CARBAZOL-4-ONE<br/>[FR] METHODE DE PREPARATION DE 1,2,3,9-TETRAHYDRO-9-METHYL-3-[(2-METHYL-1H-IMIDAZOL-1-YL)METHYL]-4H-CARBAZOL-4-ONE
  申请人：BIOGAL GYOGYSZERGYAR

  公开号：WO2003093281A1

  公开（公告）日：2003-11-13

  A process for preparing ondansetron by transamination of an ondansetron structural analog that can be readily prepared conveniently by a Mannich reaction is provided. The process represents an improvement upon known procedures for making ondansetron by transamination because of its rapid rate, selectivity and the ease with which the product can be isolated from the reaction mixture.

  提供一种通过转氨基化反应制备奥昔替尼的方法，该方法可通过Mannich反应方便地制备奥昔替尼结构类似物。该方法改进了已知的通过转氨基化反应制备奥昔替尼的程序，因为其反应速率快、选择性高，并且易于从反应混合物中分离出产物。