8-氯-1-苯基-1H-1,5-苯并二氮杂卓-2,4(3h,5h)-二酮 | 22316-55-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 8-氯-1-苯基-1H-1,5-苯并二氮杂卓-2,4(3h,5h)-二酮
• 中文别名: 氯巴占EP杂质A
• 英文名称: N-desmethylclobazam
• 英文别名: norclobazam；NDMC；1-phenyl 8-chloro 1,2,4,5-tetrahydro 2,4-dioxo 3H-1,5-benzodiazepine；7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione
• CAS: 22316-55-8
• 化学式: C₁₅H₁₁ClN₂O₂
• 分子量: 286.718
• InChiKey: RRTVVRIFVKKTJK-UHFFFAOYSA-N

物化性质

• 熔点：
  >239°C (dec.)
• 沸点：
  601.8±55.0 °C(Predicted)
• 密度：
  1.363±0.06 g/cm3(Predicted)
• 闪点：
  2℃
• 溶解度：
  乙腈（可溶）
• 碰撞截面：
  161.7 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

N-去甲基氯巴占是氯巴占的人体已知代谢物。

N-desmethylclobazam is a known human metabolite of clobazam.

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2933990090
• WGK Germany：
  3
• 储存条件：
  -20°C，密封保存，并确保干燥。

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : N-Desmethylclobazam
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]
Flammable liquids (Category 2)
Acute toxicity, Oral (Category 4)
Acute toxicity, Inhalation (Category 4)
Eye irritation (Category 2)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Highly flammable. Harmful by inhalation, in contact with skin and if swallowed. Irritating to eyes.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Danger
Hazard statement(s)
H225 Highly flammable liquid and vapour.
H302 + H332 Harmful if swallowed or if inhaled
H319 Causes serious eye irritation.
Precautionary statement(s)
P210 Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
Supplemental Hazard none
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R11 Highly flammable.
R20/21/22 Harmful by inhalation, in contact with skin and if swallowed.
R36 Irritating to eyes.
S-phrase(s)
S16 Keep away from sources of ignition - No smoking.
S36/37 Wear suitable protective clothing and gloves.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Mixtures
Component Classification Concentration
Acetonitrile
CAS-No. 75-05-8 Flam. Liq. 2; Acute Tox. 4; Eye 50 - 100 %
EC-No. 200-835-2 Irrit. 2; H225, H302 + H312 +
Index-No. 608-001-00-3 H332, H319
Registration number 01-2119471307-38-XXXX
F, Xn, R11 - R20/21/22 - R36
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

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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. Consult a physician.
In case of eye contact
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
If swallowed
Do NOT induce vomiting. 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.
Treat as cyanide poisoning., Always have on hand a cyanide first-aid kit, together with proper instructions.,
The onset of symptoms is generally delayed pending conversion to cyanide., Nausea, Vomiting, Diarrhoea,
Headache, Dizziness, Rash, Cyanosis
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
no data available
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
Use water spray to cool unopened containers.

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation.
Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapours accumulating to
form explosive concentrations. Vapours can accumulate in low areas.
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
Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and
place in container for disposal according to local regulations (see section 13).
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 inhalation of vapour or mist.
Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic
charge.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Containers which are
opened must be carefully resealed and kept upright to prevent leakage.
Recommended storage temperature: -20 °C
Specific end use(s)
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
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
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, Flame retardant antistatic protective clothing, 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 respirator
with multi-purpose combination (US) or type ABEK (EN 14387) 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: liquid
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 81 - 82 °C at 1,013 hPa81 - 82 °C at 1,013 hPa
boiling range
g) Flash point 2 °C - closed cup2 °C - closed cup
h) Evaporation rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower Upper explosion limit: 16 %(V)
flammability or 16 %(V)
explosive limits Lower explosion limit: 4,4 %(V)4,4 %(V)
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density 0,782 g/cm3 at 20 °C0,782 g/cm3 at 20 °C
n) Water solubility no data available
o) Partition coefficient: n- no data available
octanol/water
p) Auto-ignition 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
Heat, flames and sparks. Extremes of temperature and direct sunlight.
Incompatible materials
acids, Bases, Oxidizing agents, Alkali metals
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
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 Harmful if inhaled. May cause respiratory tract irritation.
Ingestion Harmful if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes Causes serious eye irritation.
Signs and Symptoms of Exposure
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Treat as cyanide poisoning., Always have on hand a cyanide first-aid kit, together with proper instructions.,
The onset of symptoms is generally delayed pending conversion to cyanide., Nausea, Vomiting, Diarrhoea,
Headache, Dizziness, Rash, Cyanosis
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
Burn in a chemical incinerator equipped with an afterburner and scrubber but exert extra care in igniting
as this material is highly flammable. Offer surplus and non-recyclable solutions to a licensed disposal
company.
Contaminated packaging
Dispose of as unused product.

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Section 14. TRANSPORT INFORMATION
UN number
ADR/RID: 1648 IMDG: 1648 IATA: 1648
UN proper shipping name
ADR/RID: ACETONITRILE, SOLUTION
IMDG: ACETONITRILE, SOLUTION
IATA: Acetonitrile, SOLUTION
Transport hazard class(es)
ADR/RID: 3 IMDG: 3 IATA: 3
Packaging group
ADR/RID: II IMDG: II IATA: II
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
N/A

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

N-去甲基卡巴佐胺是卡巴佐胺的主要活性代谢物，主要通过细胞色素P450同工酶3A4的作用生成。

反应信息

• 作为反应物：
  描述：

  8-氯-1-苯基-1H-1,5-苯并二氮杂卓-2,4(3h,5h)-二酮 在 四氯化钛 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 172.0h， 生成 8-Chloro-4-(dimethylamino)-3-(dimethylaminomethylidene)-1-phenyl-1,5-benzodiazepin-2-one
  参考文献：
  名称：

  [EN] DERIVATIVES OF L-PLIENYL-1.5-DILIYDIO-BENZO[B] [1.4]DIAZEPINE-2.4-DIONE AS INHIBITORS OF HIV REPLICATION
  [FR] DÉRIVÉS DE 1-PHÉNYL-1,5-DIHYDRO-BENZO[B] [1.4]DIAZÉPINE-2.4-DIONE EN TANT QU'INHIBITEURS DE LA RÉPLICATION DU VIH

  摘要：

  公开号：

  WO2011100838A9
• 作为产物：
  描述：

  3,4-二硝基氯苯 在 盐酸 、 五氯化磷 、 锌 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 生成 8-氯-1-苯基-1H-1,5-苯并二氮杂卓-2,4(3h,5h)-二酮
  参考文献：
  名称：

  摘要：

  DOI：

文献信息

• 一种适合工业化生产氯巴占的方法
  申请人：安徽恒星制药有限公司

  公开号：CN106243050B

  公开（公告）日：2019-09-06

  本发明公开了一种工业化生产氯巴占的方法，属于药物合成技术领域。该方法以5‑氯‑2‑硝基联苯胺为起始原料，通过在纳米重金属颗粒催化剂下还原、路易斯酸催化缩合、甲基化及精制制得了符合临床药用的氯巴占。本发明解决了现有技术毒性大、污染严重的问题，有利于劳动保护，降低了生产成本，提高了产品质量及经济效益。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF CLOBAZAM AND ITS INTERMEDIATE<br/>[FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION DE CLOBAZAM ET SON INTERMÉDIAIRE
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2016151464A1

  公开（公告）日：2016-09-29

  The present invention provides an improved process for the preparation of 8-chloro-1-phenyl- 1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione (hereafter referred to as the compound (IV)), which is useful as a key intermediate for the synthesis of Clobazam (referred to as the compound (I)) 7-chloro-1-methyl-5-phenyl-1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione. The process of the present invention further involves transformation of the compound (IV) into Clobazam (I), comprising (a) reacting the compound (II) (as described herein) with monoalkyl malonate in the presence of a coupling agent to obtain the compound (III) (as described herein); followed by the cyclization using a base; (b) reacting the compound-IV (as described herein) obtained from step (a) with methylating agent. The process of the present invention involves formation of novel intermediates methyl 3-((4- chloro-2-(phenylamino)phenyl)amino)-3-oxopropanoate (IlIa) and 3-((4-chloro-2- (phenylamino)phenyl)amino)-3-oxopropanoic acid (V).

  本发明提供了一种改进的制备8-氯-1-苯基-1H-苯并[b][1,4]二氮杂环-2,4(3H,5H)-二酮（以下简称为化合物（IV））的过程，该过程用作合成氯硝安（简称为化合物（I））7-氯-1-甲基-5-苯基-1H-苯并[b][1,4]二氮杂环-2,4(3H,5H)-二酮的关键中间体。本发明的过程还涉及将化合物（IV）转化为氯硝安（I），包括(a)在偶联剂存在下将化合物（II）（如本文所述）与单烷基马隆酸酯反应，以获得化合物（III）（如本文所述）；随后使用碱进行环化；(b)将从步骤(a)中获得的化合物-IV（如本文所述）与甲基化试剂反应。本发明的过程涉及新型中间体甲基3-((4-氯-2-(苯胺基)苯基)氨基)-3-氧代丙酸酯（IlIa）和3-((4-氯-2-(苯胺基)苯基)氨基)-3-氧代丙酸（V）的形成。
• [EN] PROCESS FOR PREPARING CLOBAZAM USING NOVEL INTERMEDIATES<br/>[FR] PROCÉDÉ DE PRÉPARATION DE CLOBAZAM À L'AIDE DE NOUVEAUX INTERMÉDIAIRES
  申请人：AMNEAL PHARMACEUTICALS COMPANY GMBH

  公开号：WO2016193482A1

  公开（公告）日：2016-12-08

  Processes for preparation of 7-chloro-1-methyl-5-phenyl-1,5-dihydro- benzo[b][1,4]diazepine-2,4-dione (Clobazam) are provided. The present invention also relates to the novel intermediates and its use in preparation of clobazam.

  提供了制备7-氯-1-甲基-5-苯基-1,5-二氢-苯并[b][1,4]二氮杂环己-2,4-二酮（氯硝安）的方法。本发明还涉及新型中间体及其在氯硝安制备中的用途。
• 1,5-Benzodiazepine-2,4-diones
  申请人：Roussel-UCLAF

  公开号：US03984398A1

  公开（公告）日：1976-10-05

  This invention relates to substituted 1,5-benzodiazepines having the formula ##SPC1## Wherein R.sub.1 and R.sub.2 are hydrogen or substituents, R.sub.3 is hydrogen or substituents, R.sub.4 is methyl or aryl group, As well as the process of producing the same. The compounds of the invention are tranquillizing analgesic, antipyretic and anti-inflammatory agents.

  本发明涉及具有式##SPC1##的取代1,5-苯并二氮杂卓，其中R1和R2为氢或取代基，R3为氢或取代基，R4为甲基或芳基，以及其制备方法。本发明的化合物是镇静止痛、退热和抗炎药物。
• 4H-S-Triazolo[4,3-2][1,5]benzodiazepin-5-ones
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04133809A1

  公开（公告）日：1979-01-09

  Compounds of the following formula ##STR1## are useful as central nervous system depressants, tranquilizers, sedatives, growth promotors, anti-convulsants and muscle relaxants in mammalian species.

  以下式的化合物对哺乳动物物种具有镇静剂、镇定剂、安眠剂、生长促进剂、抗惊厥剂和肌肉松弛剂的作用。

表征谱图