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Zhishang Chemical

4-Chloro-7-Methoxyquinoline-6-CarboxaMide CAS 417721-36-9

Molecular Formula: C11H9ClN2O2

Formula Weight: 236.65

ZSpharmac: 4-Chloro-7-Methoxyquinoline-6-CarboxaMide Supplement

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Product Name: 4-Chloro-7-Methoxyquinoline-6-CarboxaMide
CAS No: 417721-36-9
Purity: 99%

Basic Info

Product Name:4-Chloro-7-Methoxyquinoline-6-CarboxaMide
Other Names:4-chloro-7-Methoxyquinoline-6-carboxaMide
CAS:417721-36-9
Place of Origin:Shandong, China
Brand Name:ZSpharmac
Type:Pharmaceutical Intermediates
Appearance:White Solid
EINECS No.:000-000-0
Storage:Under Inert Gas (nitrogen or Argon) at 2-8°C
Provide:4-Chloro-7-Methoxyquinoline-6-CarboxaMide MSDS;
4-Chloro-7-Methoxyquinoline-6-CarboxaMide COA

What is 4-Chloro-7-Methoxyquinoline-6-CarboxaMide?

4-Chloro-7-methoxyquinoline-6-amide is a pharmaceutical intermediate used in the preparation of lenvatinib (E7080). Lenvatinib is an oral multi-receptor tyrosine kinase inhibitor developed by Eisai, which is a potential treatment for thyroid cancer, liver cancer, non-small cell lung cancer and other solid tumors.

4-Chloro-7-Methoxyquinoline-6-CarboxaMide Properties:

Boiling point 426.7±45.0 °C(Predicted)
density 1.380±0.06 g/cm3(Predicted)
storage temp. under inert gas (nitrogen or Argon) at 2-8°C
pka15.28±0.30(Predicted)
CAS DataBase Reference417721-36-9

 

4-Chloro-7-Methoxyquinoline-6-CarboxaMide Uses

  1. 4-Chloro-7-methoxyquinoline-6-amide is mainly used as a lenvatinib intermediate.
  2. 4-Chloro-7-methoxyquinoline-6-amide is a pharmaceutical intermediate used in the preparation of lenvatinib (E7080). Lenvatinib is an oral multi-receptor tyrosine kinase inhibitor developed by Eisai Co., Ltd., and is a potential treatment for thyroid cancer, liver cancer, non-small cell lung cancer and other solid tumors.

Preparation of 4-Chloro-7-Methoxyquinoline-6-Amide

Step 1, the synthesis of 4-cyano-3-methoxyaniline: take 134g of 4-cyano-3-hydroxyaniline, dissolve it in 500mL of N,N-dimethylformamide (DMF) and mix it well, then take 300g of the mixture , 32g of tetrabutylammonium bromide and 268g of potassium carbonate were added, the temperature of the reaction system was raised to 110°C, and 100g of dimethyl carbonate was added dropwise. After the dropwise addition, the reaction was continued for 8h. After the reaction was completed, it was cooled to room temperature, filtered, and the filtrate was reduced The solvent was distilled off under pressure, 200 g of water was added, and 500 mL of ethyl acetate was added for extraction. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was recovered from the filtrate. The volume ratio was 1:1300 to obtain 139 g of a pale yellow solid.
Step 2: Synthesis of oxime: take 74 g of the product of the first step, 4-cyano-3-methoxyaniline, dissolve in ethanol, heat to reflux, add 50 g of propionic acid dropwise, and continue to react for 5 h after the dropwise addition is completed. After the completion, the solvent was recovered under reduced pressure, and the product continued to the next step without separation.
Step 3, Synthesis of 6-cyano-7-methoxy-4-quinolinone: add 100 mL of polyphosphoric acid to the residue of the previous step, heat up to 90°C and react for 10 hours. After the reaction is completed, the reaction system is cooled After reaching room temperature, the reaction solution was poured into ice water under an ice bath, stirred vigorously for 2 h, a large amount of white solid was precipitated, filtered, and the filter cake was washed with water until neutral, and dried in vacuo to obtain 91 g of white solid.
Step 4. Synthesis of 6-cyano-7-methoxy-4-chloroquinoline: take 50 g of 6-cyano-7-methoxy-4-quinolinone, dissolve in 80 mL of thionyl chloride, heat up The reaction was refluxed for 5h. After the reaction, the unreacted thionyl chloride was recovered under reduced pressure. The residue was poured into ice water, stirred for 1h, filtered, and the filter cake was washed with water until neutral, and dried in vacuo to obtain 52g of white solid powder.
Step 5. Synthesis of 4-chloro-7-methoxyquinoline-6-amide: take 218 g of 6-cyano-7-methoxy-4-chloroquinoline, dissolve in acetic acid solution, wherein glacial acetic acid and water The volume ratio was 1:1500, heated to 80 °C for 24 hours, after the reaction, the reaction system was cooled to room temperature, 500 mL of ice water was added to the system, stirred overnight, a large amount of solid was precipitated, filtered, and the filter cake was washed with water until neutral, and dried. 222g of white solid.

4-Chloro-7-methoxyquinoline-6-amide application

The procedure for preparing lenvatinib using 4-chloro-7-methoxyquinoline-6-amide is as follows:
Take 2.36 g of 4-chloro-7-methoxyquinoline-6-amide, 2.3 g of 1-(2-chloro-4-hydroxyphenyl)-3-cyclopropylurea, 5 mL of 20% sodium methoxide solution, chloroform 20mL, heated and refluxed for 5h, after the reaction was completed, cooled to room temperature, the reaction solution was poured into ice water, separated, the organic layer was washed with water until neutral, dried over anhydrous sodium sulfate, filtered, and the filtrate was decompressed to recover the solvent to obtain crude product, crude product It was recrystallized from acetone-water to obtain 3.9 g of lenvatinib as a white solid.

4-Chloro-7-methoxyquinoline-6-amide first aid measures

If inhaled
Move victim to fresh air. If breathing is difficult, give oxygen. If not taking a breath, offer artificial respiration and look for medical interest right away.Do not use mouth-to-mouth resuscitation if the victim has ingested or inhaled the chemical.
After skin contact
Take off contaminated clothing immediately. Wash with soap and plenty of water. Consult a doctor.
after eye contact
Rinse with purified water for at least 15 minutes. Consult a doctor.
After ingestion
Rinse mouth with water. Do not induce vomiting. Never give an unconscious person anything from the mouth. ” Call a medical professional or poisonous substance control center right now.”

4-Chloro-7-Methoxyquinoline-6-Amide Experimental Operation

1) Ammonia (200 mL, 5.2 mol) was added to a 500 mL three-necked flask, and compound IV (10 g, 39.8 mmol) obtained in step 3.3) was added to obtain mixture H;
2) The mixture H obtained in step 4.1) was placed at 60° C. After 4 hours of reaction, the mixture was cooled to room temperature to obtain mixture I; 4.3) Dichloromethane was added to mixture I, and extracted 3 times to obtain pale yellow compound V (yield 85.17%)
Methyl 4-chloro-7-methoxy-quinoline-6-carboxylate (120 mg) was dissolved in methanol (6 ml), 28% aqueous ammonia (6 ml) was added, and the mixture was stirred at 40°C overnight. The solvent was distilled off under reduced pressure, and the residue was purified by methanol-chloroform thin-layer chromatography to obtain 4-chloro-7-methoxy-quinoline-6-carboxamide (91 mg, yield 80%). 4-Chloro-7 -Methoxy-quinoline-6-carboxylic acid amide (91 mg), 5,6-dimethyl-[2,2′]bipyridin-3-ol (115 mg) and 4-dimethylaminopyridine (141 mg) was dissolved in dimethyl sulfoxide (3 ml), cesium carbonate (375 mg) was added to the solution, and the mixture was stirred at 130° C. overnight. The mixture was cooled to room temperature and water was added to the reaction mixture. The organic layer was extracted with chloroform, and the chloroform layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by thin-layer chromatography with a methanol-chloroform system to obtain the title compound (33 mg, yield 22%). 1H-NMR (CDCl3, 400 MHz): δ 2.40 (s, 3H), 2.67 (s, 3H), 4.13 (s, 3H), 5.92 (m, 1H), 6.39 (d, J = 5.4 Hz, 1H) , 7.08 (ddd, J = 1.2, 4.9, 7.6 Hz, 1H), 7.36 (s, 1H), 7.56 – 7.63 (m, 2H), 7.76 (m, 1H), 7.90 (m, 1H), 8.40 (m , 1H), 8.54 (d, J = 5.6 Hz, 1H), 9.27 (d, J = 1.0 Hz, 1H) Mass spectrum (ESI-MS, m/z): 423 (M+Na)+.

Company Profile and Corporate Culture

Company Profile:

ZhiShang Chemical is owned by ZhiShang Group is a professional new-type chemicals enterprise combined into research and development, production and sales .

The company’s competitive product is pharmaceutical raw materials and intermediates (especially carbohydrate derivatives Series), In recent years, the company has made a major breakthrough in food and feed additives, plant extraction, industrial chemicals industry .

The company insists on the spirit of “sincere management, strict quality control, customer as god” , get consistent high praise from customers at home and abroad.

Corporate Culture:

OUR MISSION

Help China Chemicals to benefit the happiness of human life

OUR VISION

Become the most trusted chemical supplier in the world

OUR BUSINESS PHILOSOPHY

Striver – oriented, enrich employees, customer first, deep service, seek development

OUR VALUES

Be prepared for danger in times of peace, forge ahead actively, unity and cooperation, and be brave to fight

About Us

The production base is located in Zhangqiu chemical industry park and Tai’an high-tech chemical industry park. laboratory and workshop in strict accordance with the GMP standard and the product fit national ISO9001 and ISO2000 standards.

“Zhishang” products are exported to Europe, North and South America, the Middle East, Asia Pacific and Africa area, so as to establish a long-term and stable cooperation relationship with customer in the world.

Company Info
  • Business Type: Manufacturer
  • Product Range: Additive , Chemical Auxiliary & Catalyst , Organic Chemicals
  • Products/Service: Organic Intermediate,Inorganic Chemistry, APIs, Dyestuffs And Pigments, Fragrance And Spices, Food Additives
  • Total Employees: 51~100
  • Capital (Million US $): 10000000RMB
  • Year Established: 2016
Production Capacity
  • No. of Production Lines : 8
  • No. of QC Staff : 5 -10 People
  • OEM Services Provided : yes
  • Factory Size (Sq.meters) : 3,000-5,000 square meters
  • Certificate: ISO9001 , CE , GMP , API , MSDS
  • Factory Location : Diao Town Industry Park, Zhangqiu City, Jinan City, Shandong Province, China.

Service

Pre-Sales Service

* Prompt reply and 24 hours online, professional team to provide best price and high quality product.

* Sample testing support.

* Every batch of products will be tested to ensureits quality.

*The packing also can be according the customers` requirment.

*Any inquiries will be replied within 24 hours.

*we provide Commerical Invoice, Packing List, Bill of loading, COA , Health certificate and Origin certificate. If your markets have any special requirements, let us know.

 

After-Sales Service

*The fact of logistics information monitoring.

* Any questions about the product can be consulted at any time.

*Product has any problem can return.

FAQ

Do you accept sample order?

We will make samples before mass production, and after sample approved, we’ll begin mass production. Doing 100% inspection during production, then do random inspection before packing.

 

HOW TO CONFIRM THE PRODUCT QUALITY BEFORE PLACING ORDERS?

You can get free samples for some products,you only need to pay the shipping cost or arrange a courier to us and take the samples. You can send us your product specifications and requests,we will manufacture the products according to your requests.

What’s your MOQ?

Our MOQ is 1kg. But usually we accept less quantity such as 100g on the condition that sample charge is 100% paid.

Do you supply product report?

Yes. We’ll give you product analysis report before shipping.

  Is there a discount?

Different quantity has different discount.

Shipping

1. ≤50kg, Express delivery recommended, usually called as DDU service;

2. ≤500kg, Air shipping recommended, usually called as FOB, CFR, or CIF service;

3. >500kg, sea shipping recommended, usually called as FOB, CFR, or CIF service;

4. For high value products, please select air shipping and express delivery for safe.

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