4-(4-氟苯基)-6-异丙基-2-[(N-甲基-N-甲磺酰)氨基]嘧啶-5-甲醛 | 147118-37-4

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-(4-氟苯基)-6-异丙基-2-[(N-甲基-N-甲磺酰)氨基]嘧啶-5-甲醛
• 中文别名: 罗素伐他汀钙中间体R-1-3；嘧啶甲醛；4-(4-氟苯基)-6-异丙基-2-(N-甲基-N-甲磺酰胺基)-5-甲酰基-1-嘧啶；4-(4-氟苯基)-6-异丙基-2-(N-甲基-N-甲磺酰基氨基)嘧啶-5-甲醛；4-(4-氟苯基)-6-异丙基-2-(N-甲基-N-甲磺酰基氨基)-5-嘧啶甲醛；瑞舒伐他汀钙中间体三；罗素伐他汀钙中间体 R-1-3；N-[4-(4-氟苯基)-5-甲醛基-6-异丙基-2-嘧啶基]-N-甲基甲磺酰胺；Z-8；4-(4-氟苯基)-6-异丙基-2-((N-甲基-N-甲磺酰)氨基)嘧啶-5-甲醛；瑞舒伐他汀钙中间体Z-8
• 英文名称: N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide
• 英文别名: 4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-methanesulfonamido)-5-pyrimidinecarbaldehyde；4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonamido)pyrimidin-5-yl-formaldehyde；4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidine-5-carbaldehyde；N-(4-(4-Fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide；N-[4-(4-fluorophenyl)-5-formyl-6-propan-2-ylpyrimidin-2-yl]-N-methylmethanesulfonamide
• CAS: 147118-37-4
• 化学式: C₁₆H₁₈FN₃O₃S
• mdl: MFCD08458342
• 分子量: 351.402
• InChiKey: WOCOTUDOVSLFOB-UHFFFAOYSA-N

物化性质

• 熔点：
  178.0 to 182.0 °C
• 沸点：
  536.6±60.0 °C(Predicted)
• 密度：
  1.320±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（非常轻微，加热）

计算性质

• 辛醇/水分配系数(LogP)：
  2.59
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.312
• 拓扑面积：
  80.23
• 氢给体数：
  0.0
• 氢受体数：
  5.0

安全信息

• 海关编码：
  2935009090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  Refrigerator

SDS

4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N- Revision number: 5
methanesulfonylamino)-5-pyrimidinecarboxaldehyde
SAFETY DATA SHEET

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Section 1. IDENTIFICATION
Product name: 4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino)-5-
pyrimidinecarboxaldehyde

Revision number: 5

---

Section 2. HAZARDS IDENTIFICATION
GHS classification
Not classified
PHYSICAL HAZARDS
HEALTH HAZARDS Not classified
Not classified
ENVIRONMENTAL HAZARDS
GHS label elements, including precautionary statements
Pictograms or hazard symbols None
Signal word No signal word
Hazard statements None
Precautionary statements: None

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substance/mixture: Substance
4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino)-5-
Components:
pyrimidinecarboxaldehyde
>98.0%(LC)(N)
Percent:
CAS Number: 147118-37-4
Chemical Formula: C16H18FN3O3S

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Section 4. FIRST AID MEASURES
Remove victim to fresh air and keep at rest in a position comfortable for breathing.
Inhalation:
Get medical advice/attention if you feel unwell.
Remove/Take off immediately all contaminated clothing. Rinse skin with
Skin contact:
water/shower. If skin irritation or rash occurs: Get medical advice/attention.
Rinse cautiously with water for several minutes. Remove contact lenses, if present
Eye contact:
and easy to do. Continue rinsing. If eye irritation persists: Get medical
advice/attention.
Ingestion: Get medical advice/attention if you feel unwell. Rinse mouth.
Protection of first-aiders: A rescuer should wear personal protective equipment, such as rubber gloves and air-
tight goggles.

---

Section 5. FIRE-FIGHTING MEASURES
Suitable extinguishing Dry chemical, foam, water spray, carbon dioxide.
media:
Specific hazards arising Take care as it may decompose upon combustion or in high temperatures to
generate poisonous fume.
from the chemical:
4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-
methanesulfonylamino)-5-
pyrimidinecarboxaldehyde

---

Section 5. FIRE-FIGHTING MEASURES
Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing
method according to the surrounding situation is used. Uninvolved persons should
evacuate to a safe place. In case of fire in the surroundings: Remove movable
containers if safe to do so.
Special protective When extinguishing fire, be sure to wear personal protective equipment.
equipment for firefighters:

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Section 6. ACCIDENTAL RELEASE MEASURES
Use personal protective equipment. Keep people away from and upwind of spill/leak.
Personal precautions,
protective equipment and Entry to non-involved personnel should be controlled around the leakage area by
emergency procedures: roping off, etc.
Environmental precautions: Prevent product from entering drains.
Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it.
containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with
up: appropriate laws and regulations.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Technical measures: Handling is performed in a well ventilated place. Wear suitable protective equipment.
Prevent dispersion of dust. Wash hands and face thoroughly after handling.
Use a local exhaust if dust or aerosol will be generated.
Advice on safe handling: Avoid contact with skin, eyes and clothing.
Conditions for safe storage, including any
incompatibilities
Storage conditions: Keep container tightly closed. Store in a cool and dark place.
Store away from incompatible materials such as oxidizing agents.
Packaging material: Comply with laws.

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Section 8. EXPOSURE CONTROLS / PERSONAL PROTECTION
Install a closed system or local exhaust as possible so that workers should not be
Engineering controls:
exposed directly. Also install safety shower and eye bath.
Personal protective equipment
Respiratory protection: Dust respirator. Follow local and national regulations.
Protective gloves.
Hand protection:
Eye protection: Safety glasses. A face-shield, if the situation requires.
Skin and body protection: Protective clothing. Protective boots, if the situation requires.

---

Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Physical state (20°C): Solid
Form: Crystal- Powder
White - Almost white
Colour:
Odour: No data available
pH: No data available
Melting point/freezing point:180°C
No data available
Boiling point/range:
Flash point: No data available
Flammability or explosive
limits:
No data available
Lower:
Upper: No data available
Relative density: No data available
Solubility(ies):
No data available
[Water]
[Other solvents]
Hot acetone
Soluble:
4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-
methanesulfonylamino)-5-
pyrimidinecarboxaldehyde

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Section 10. STABILITY AND REACTIVITY
Chemical stability: Stable under proper conditions.
Possibility of hazardous No special reactivity has been reported.
reactions:
Incompatible materials: Oxidizing agents
Hazardous decomposition Carbon monoxide, Carbon dioxide, Nitrogen oxides (NOx), Hydrogen fluoride, Sulfur
products: oxides

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Section 11. TOXICOLOGICAL INFORMATION
Acute Toxicity: No data available
Skin corrosion/irritation: No data available
Serious eye No data available
damage/irritation:
Germ cell mutagenicity: No data available
Carcinogenicity:
IARC = No data available
No data available
NTP =
Reproductive toxicity: No data available

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Section 12. ECOLOGICAL INFORMATION
Ecotoxicity:
Fish: No data available
Crustacea: No data available
Algae: No data available
Persistence / degradability: No data available
Bioaccumulative No data available
potential(BCF):
Mobility in soil
Log Pow: No data available
Soil adsorption (Koc): No data available
Henry's Law No data available
constant(PaM3/mol):

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Section 13. DISPOSAL CONSIDERATIONS
Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system.
Observe all federal, state and local regulations when disposing of the substance.

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Section 14. TRANSPORT INFORMATION
Hazards Class: Does not correspond to the classification standard of the United Nations
UN-No: Not listed

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Section 15. REGULATORY INFORMATION
Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002
and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport,
loading and unloading were prescribed.
4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-
methanesulfonylamino)-5-
pyrimidinecarboxaldehyde

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

应用的化合物4-(4-氟苯基)-6-异丙基-2-[(N-甲基-N-甲磺酰)氨基]嘧啶-5-甲醛是瑞舒伐他汀钙的重要中间体。瑞舒伐他汀钙（Rosuvastatin Calcium）是一种由日本盐野义公司开发的新型降血脂药物，化学名称为(+)-(3R,5S)-7-[4-(4-氟苯基)-6-异丙基-2-(N-甲基-N-甲磺酰胺基)嘧啶-5-基]-3,5-二羟基-6(E)-庚烯酸钙(I)。该药物属于HMG-CoA还原酶抑制剂，能够降低低密度胆固醇、总胆固醇、甘油三酯和脱辅酶基蛋白B浓度，并提高高密度胆固醇的浓度。

制备

1. 嘧啶醇(III) 的合成： 向100mL三口烧瓶中加入50mL四氢呋喃、2.3g（60mmol）硼氢化钠和7.6g（20mmol，HPLC纯度99.7%）嘧啶酯(II)。降温至-20℃，缓慢滴加34.8g（120mmol）三氟化硼四氢呋喃络合物，升温至65℃保温反应24h。反应完毕后，冷却至室温，向反应液中缓慢加入盐酸(v/v=5%)，搅拌0.5h后，再加入饱和的NaHCO3调pH值为7～8。使用CH2Cl2(20mL×2)萃取，分去水层，用无水硫酸钠搅拌干燥，过滤，滤液减压浓缩至干，得到浅黄色固体嘧啶醇(III)6.78g，收率96.0%。

2. 嘧啶醛(IV) 的合成： 在100mL三口瓶中加入上述步骤制得的4-(4-氟苯基)-2-羟基-6-异丙基-5-甲氧羰基-2-(N-甲基-N-甲烷磺酰胺基)嘧啶-5-甲醇17.65g（50mmol）、0.187g TEMPO（1.2mmol）和0.606g Fe(NO3)3·9H2O（1.5mmol），并加入15mL二氯甲烷。通入氧气，在20℃下搅拌反应24h，通过TLC监测反应进程。反应结束后，向反应液中加入30mL水，静置分层、分液，并使用二氯甲烷(20mL×2)萃取，合并有机相，减压蒸除有机溶剂，得到白色固体嘧啶醛(IV)17.23g，收率98.2%。

反应信息

• 作为反应物：
  描述：

  4-(4-氟苯基)-6-异丙基-2-[(N-甲基-N-甲磺酰)氨基]嘧啶-5-甲醛 在 盐酸 、 水 、 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 生成 罗伐他汀
  参考文献：
  名称：

  [EN] PROCESSES FOR THE PREPARATION OF ROSUVASTATIN OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
  [FR] PROCÉDÉ DE PRÉPARATION DE ROSUVASTATINE OU DE SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELLE-CI

  摘要：

  本发明涉及制备式I的瑞舒伐他汀钙及其药学上可接受的盐的新型中间体的过程，以及含有该物质的药物组合物。

  公开号：

  WO2016125086A1
• 作为产物：
  描述：

  2-氟苯乙酮 在 sodium ethanolate 、 三乙胺 、 N,N-二甲基甲酰胺 、 potassium hydroxide 、 三氯氧磷 作用下， 以 异丙醇 、 丙酮 、 甲苯 为溶剂， 反应 18.0h， 生成 4-(4-氟苯基)-6-异丙基-2-[(N-甲基-N-甲磺酰)氨基]嘧啶-5-甲醛
  参考文献：
  名称：

  一种合成瑞舒伐他汀钙关键中间体的方法

  摘要：

  本发明公开了一种合成瑞舒伐他汀钙中间体式I方法，其反应路线如下所示：本发明方法使用原料毒性低，所用溶剂可以同步回收，且没有使用到4‑甲基吗啉‑N‑氧化物、TPAP（过钌酸四丙基铵）、DIBAL‑H等非常昂贵的物料，有效降低了生产成本；反应条件温和，能耗低，不需要特殊的反应设备，而且操作简单，可实现一锅进行，易于规模化生产。

  公开号：

  CN105712939B
• 作为试剂：
  描述：

  (R)-3-((tert-butyldimethylsilyl)oxy)-5-oxo-N-((R)-1-phenylethyl)-6-(triphenyl-l5-phosphanylidene)hexanamide 、 4-(4-氟苯基)-6-异丙基-2-[(N-甲基-N-甲磺酰)氨基]嘧啶-5-甲醛 在 4-(4-氟苯基)-6-异丙基-2-[(N-甲基-N-甲磺酰)氨基]嘧啶-5-甲醛 作用下， 以71.8的产率得到(3R,6E)-3-[(tert-butyldimethylsilyl)oxy]-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-5-oxo-N-[(1R)-1-phenylethyl]hept-6-enamide
  参考文献：
  名称：

  瑞舒伐他汀钙中间体及制备瑞舒伐他汀钙中间体和瑞舒伐他汀钙的方法

  摘要：

  瑞舒伐他汀钙中间体及制备瑞舒伐他汀钙中间体和瑞舒伐他汀钙的方法，属于有机药物合成技术领域。本发明包括新颖的瑞舒伐他汀钙中间体J-4，并且包括了瑞舒伐他汀钙中间体J-4的制备方法及利用瑞舒伐他汀钙中间体J-4制备瑞舒伐他汀钙的方法。本发明合成路线较短、收率较高，且原料低廉易的，非常适合产业化。

  公开号：

  CN102358747A

文献信息

• Metal-free, visible-light photoredox catalysis: transformation of arylmethyl bromides to alcohols and aldehydes
  作者：Jian Li、Hongni Wang、Li Liu、Jiangtao Sun

  DOI：10.1039/c4ra09190f

  日期：——

  A mild, simple, and controllable metal-free photocatalytic system for the transformation of arylmethyl bromides to corresponding alcohols and aldehydes in high yields with visible-light irradiation has been achieved. Eosin Y was found to be an efficient promoter for this oxidative dehalogenation reaction under photo irradiation conditions.

  已实现一种温和、简单且可控的无金属光催化系统，通过可见光照射，在高产率下将芳甲基溴转化为相应的醇和醛。研究表明，曙红Y在光照射条件下是该氧化脱卤反应的高效促进剂。
• A Simple, Mild and General Oxidation of Alcohols to Aldehydes or Ketones by SO ₂ F ₂ /K ₂ CO ₃ Using DMSO as Solvent and Oxidant
  作者：Gao‐Feng Zha、Wan‐Yin Fang、Jing Leng、Hua‐Li Qin

  DOI：10.1002/adsc.201900104

  日期：2019.5.14

  A practical, general and mild oxidation of primary and secondary alcohols to carbonyl compounds proceeds in yields of up to 99% using SO2F2 as electrophile in DMSO as both the oxidant and the solvent at ambient temperature. No moisture‐ and oxygen‐free conditions are required. Stoichiometric amount of inexpensive K2CO3, which generates easy to separate by‐products, is used as the base. Thus, 5‐gram

  在环境温度下，使用SO 2 F 2作为亲电子试剂在DMSO中作为氧化剂和溶剂，伯醇和仲醇进行实用，通用且温和的氧化成羰基化合物的收率可达99％。不需要无湿气和无氧条件。化学计量的廉价K 2 CO 3生成易于分离的副产物的油基用作基础。因此，通过简单的过滤作为后处理，以几乎定量的产量进行了5克规模的运行。还应注意使用通常促进竞争的Pummerer重排的极性溶剂（例如DMSO）。该协议与（杂）芳烃，烯烃和炔烃底物上的各种常见的N-，O-和S-官能团兼容（68个例子）。该方案被应用（99％的产率）用于重要的降胆固醇药物瑞舒伐他汀的正式合成。
• Heterogeneously Catalyzed Selective Decarbonylation of Aldehydes by CeO₂-Supported Highly Dispersed Non-Electron-Rich Ni(0) Nanospecies
  作者：Takehiro Matsuyama、Takafumi Yatabe、Tomohiro Yabe、Kazuya Yamaguchi

  DOI：10.1021/acscatal.1c03375

  日期：2021.11.19

  Aldehyde decarbonylation has been extensively investigated, primarily using noble-metal catalysts; however, nonprecious-base-metal-catalyzed aldehyde decarbonylation has been hardly reported. We have established an efficient selective aldehyde decarbonylation reaction with a broad substrate scope and functional group tolerance utilizing a heterogeneous Ni(0) nanospecies catalyst supported on CeO2.

  醛脱羰已被广泛研究，主要使用贵金属催化剂；然而，几乎没有报道过非贵金属催化的醛脱羰。我们已经建立了一种有效的选择性醛脱羰反应，该反应具有广泛的底物范围和官能团耐受性，利用负载在 CeO 2上的非均相 Ni(0) 纳米物质催化剂。根据详细的催化剂表征和动力学评估，高催化性能归因于高度分散和非富电子的 Ni(0) 纳米物质，这可能抑制副反应产生酯和吸附 CO 衍生的催化转化抑制。
• Highly stereoselective hydrogenations-As key-steps in the total synthesis of statins
  作者：Natalia Andrushko、Vasyl Andrushko、Vitali Tararov、Andrei Korostylev、Gerd König、Armin Börner

  DOI：10.1002/chir.20782

  日期：2010.5.15

  Statins are inhibitors of 3‐hydroxy‐3‐methyl‐glutaryl coenzyme A reductase (HMG‐CoA reductase) and became the standard of care for treatment of hypercholesterolemia because of their efficacy, safety, and long‐term benefits. They are administered as diastereo‐ and enantiomerically pure compounds. We summarize here two new approaches for the total synthesis of the most important representatives, atorvastatin

  他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-CoA还原酶）的抑制剂，由于其功效，安全性和长期益处，已成为治疗高胆固醇血症的护理标准。它们以非对映体和对映体纯化合物的形式给药。我们在此总结了两种新方法，这些方法以高度立体选择性氢化为关键步骤，用于总合成最重要的代表阿托伐他汀和瑞舒伐他汀。手性2010。©2009 Wiley‐Liss，Inc.。
• Chemical Process
  申请人：Butters Michael

  公开号：US20080207903A1

  公开（公告）日：2008-08-28

  A process for formation of a compound of formula (I) or a pharmaceutically acceptable salt thereof, (A chemical formula should be inserted here—please see paper copy enclosed herewith) I via a Heck reaction is described. Intermediates useful in the process and processes for making said intermediates are also described.

  一种通过Heck反应形成化合物式(I)或其药用可接受盐的方法被描述。还描述了在该过程中有用的中间体以及制备所述中间体的方法。