757251-39-1

Basic information

• Product Name: 4-(4-AMINO-3-FLUOROPHENOXY)-N-METHYLPICOLINAMIDE
• Synonyms: 4-(4-AMINO-3-FLUOROPHENOXY)-N-METHYLPICOLINAMIDE;2-Pyridinecarboxamide,4-(4-amino-3-fluorophenoxy)-N-methyl-;4-(4-Amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide;4-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide;4-(4-AMINO-3-FLUOROPHENOXY)-N-METHYL-2-PYRIDINECARBOXAMIDE;4-(4-Amino-3-fluorophenoxy)-N-methylpicolinamide EINECS;4-(4-AMINO-3-FLUOROPHENOXY)-N-METHYLPICOLIMIDE;Regorafenib Intermediate
• CAS NO: 757251-39-1
• Molecular Formula: C₁₃H₁₂FN₃O₂
• Molecular Weight: 261.25
• EINECS: 1592732-453-0
• Product Categories: Regorafenib
• Mol File: 757251-39-1.mol

Chemical Properties

• Melting Point: 143 °C
• Boiling Point: 459.8°C at 760 mmHg
• Flash Point: 231.9°C
• Appearance: /
• Density: 1.305
• Vapor Pressure: 1.22E-08mmHg at 25°C
• Refractive Index: 1.602
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: Chloroform (Slightly), DMSO (Sparingly), Methanol (Slightly)
• PKA: 13.92±0.46(Predicted)
• Water Solubility: 190mg/L at 20℃
• CAS DataBase Reference: 4-(4-AMINO-3-FLUOROPHENOXY)-N-METHYLPICOLINAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(4-AMINO-3-FLUOROPHENOXY)-N-METHYLPICOLINAMIDE(757251-39-1)
• EPA Substance Registry System: 4-(4-AMINO-3-FLUOROPHENOXY)-N-METHYLPICOLINAMIDE(757251-39-1)

Safety Data

• Hazardous Substances Data: 757251-39-1(Hazardous Substances Data)

Usage

InChI:InChI=1/C13H12FN3O2/c1-16-13(18)12-7-9(4-5-17-12)19-8-2-3-11(15)10(14)6-8/h2-7H,15H2,1H3,(H,16,18)

Upstream product

• 220000-87-3 4-chloro-N-methylpicolinamide 
• 399-95-1 4-amino-3-fluorophenol 
• 108-10-1 4-methyl-2-pentanone 
• 882167-77-3 4-chloro-N-methyl-pyridine-2-carboxamide hydrochloride 
• 103842-00-8 N-(2-fluoro-4-hydroxyphenyl)acetamide 
• 176977-85-8 methyl 4-chloropyridine-2-carboxylate hydrochloride 
• 394-41-2 3-fluoro-4-nitrophenol 
• 1209459-88-0 4-bromo-pyridine-2-carboxylic acid methyl amide 
• 67-56-1 methanol 
• 755037-03-7 regorafenib 
• 1493-27-2 ortho-nitrofluorobenzene 
• 372-20-3 3-fluorophenol 
• 51727-15-2 4-chloro-2-pyridine carboxylic acid chloride hydrochloride 
• 98-98-6 2-Picolinic acid 

Downstream Products

• 755037-03-7 regorafenib 
• 835621-08-4 4-{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide mesylate 
• 835621-07-3 4-{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide hydrochloride 

Relevant articles and documents

Synthesis method of regorafenib

The invention provides a synthesis method of regorafenib, which adopts 3-fluoro-4-nitrophenol as a raw material to replace the traditional 3-fluoro-4-aminophenol to carry out etherification reaction, and then carries out catalytic hydrogenation to obtain 4-(4-amino-3-fluorophenoxy)-N-methylpyridine-2-formamide, and has the advantages that the nitro stability is much higher than the amino stability; catalytic hydrogenation is carried out after etherification with the 4-chloro-2-pyridine formamide, such that the hydroxyl group is etherified so that the product stability is improved greatly, the purity and the yield of the product obtained after the catalytic hydrogenation are substantially improved, and the quality of the final product regorafenib is ensured. 3-fluorine-4-nitrophenol is used as a starting material to be subjected to etherification reaction with 4-chlorine-2-pyridine formamide, so that 4-methyl-2-pentanone is not needed to protect amino, and the quality of an intermediate obtained after catalytic hydrogenation and the quality of a final product are better.

METHODS OF USING REBASTINIB IN THE TREATMENT OF DISORDERS

Described herein are methods of treating various disorders in patients in need thereof, comprising administering to the patient the compound of Formula (I) or a pharmaceutically acceptable salt thereof. Exemplary disorders that can be treated by the methods described herein include gynecologic carcinosarcomas, endometrial adenocarcinomas, mesotheliomas, ovarian cancers, pancreatic ductal adenocarcinomas, and lung cancers.

POLYAROMATIC UREA DERIVATIVES AND THEIR USE IN THE TREATMENT OF MUSCLE DISEASES

The current invention provides urea derivatives, in particular compounds having the core structure heteroaryl-NH-CO-NH-aryl-O- heteroaryl, for use in treating, ameliorating, delaying, curing and/ or preventing a disease or condition associated with muscle cells and/or satellite cells, such as Duchenne muscular dystrophy, Becker muscular dystrophy, cachexia or sarcopenia.

Regorafenib analogues and their ferrocenic counterparts: Synthesis and biological evaluation

Approved by the FDA in 2012, regorafenib is one of the last chance treatments for colorectal cancer. While various analogues have already been prepared, ferrocenic derivatives have never been evaluated. In this study, we prepared various ferrocene-containing derivatives of regorafenib and recorded their biological activity in kinase and cellular assays. This led to the identification of a squaramide derivative which shows a good cellular activity and three ferrocene analogues with promising activity in both kinase and cellular assays. This journal is

Substituted pyridine-2-formamide compound and application thereof

The invention belongs to the technical field of medicinal chemistry, and relates to a substituted pyridine-2-formamide compound and application thereof, wherein specifically the substituted pyridine-2-formamide compound has a structure represented by a formula I. According to the invention, based on excellent in vitro inhibition activity on VEGFR-2 kinase and PDGFR-beta kinase and HUVEC cell inhibition activity, the compound can be used as a small-molecular tyrosine kinase (especially Raf kinase) inhibitor, has the effect of inhibiting cell proliferation and angiogenesis, has good antitumor activity, and has a good effect of treating tumor diseases of mammals (including human beings).

Synthetic method of anti-cancer drug Stivarga

The invention provides a synthetic method of an anti-cancer drug Stivarga. The method comprises the steps of taking 3-fluoro-4-nitrophenol as a raw material, performing condensation reaction with N-methyl-4-chloro-2-pyridine carboxamide under the action of alkali to obtain 4-(4-nitryl-3-fluorobenzene)-2-(methyl carbamyl) pyridine, performing catalytic reduction to obtain 4-(4-amino-3-fluorobenzene)-2-(methyl carbamyl) pyridine, then performing condensation reaction with 4-chloro-3-(trifluoromethyl) phenyl isocyanate in tetrahydrofuran, so as to obtain the Stivarga. The synthetic method provided by the invention has the advantages that the adopted raw material is relatively cheap and easy to obtain, the reaction conditions are mild, the operation is simple and safe, the product yield is relatively high, the product purity is high, and the industrialization value is relatively high.

Preparation method of regorafenib hydrate

The invention belongs to the field of drug synthesis and particularly relates to a preparation method of regorafenib hydrate. 4-methyl-2-pentanone, 4-amino-3-fluorophenol and N-methyl-4-chloro-2-pyridine carboxamide are condensed to obtain a regorafenib intermediate 1, 4-chloro-3-(trifluoromethyl)isocyanate is added for condensation and salt-forming reactions to produce a regorafenib intermediate2, and finally, free hydration is performed in an alkaline acetone aqueous solution to obtain the regorafenib hydrate. The preparation method of the regorafenib hydrate is simple to operate and easy to monitor, has yield up to 90% or above and high efficiency and is applicable to mass industrial production. The prepared regorafenib hydrate has low impurity content, has no solvent residues basically, significantly shortens purification time, has stable properties, keeps stable in accelerated stability tests and has high safety.

A new pathway via intermediate 4-amino-3-fluorophenol for the synthesis of regorafenib

A practical synthetic route to regorafenib, in which the target compound was obtained via a 10-step synthesis starting from 2-picolinic acid, 4-chloro-3-(trifluoromethyl)aniline, and 3-fluorophenol, is reported. Crucial to the strategy is the preparation of 4-amino-3-fluorophenol via Fries and Beckman rearrangements using an economical and practical protocol. The main advantages of the route include inexpensive starting materials and an acceptable overall yield. A scale-up experiment was carried out to provide regorafenib with 99.96% purity in 46.5% total yield.

A process for preparing auspicious standard phinney intermediates

The invention discloses a method for preparing a regorafenib intermediate; a compound represented by the formula II and a compound represented by the formula III are subjected to three stages of a step A, a step B and a step C, intermediates of all the stages are not separated, and thus the regorafenib intermediate I is prepared. According to the method, the intermediates of all the steps are not separated, post-treatment procedures are reduced, the process operational flow is saved, the solvent recovery and utilization efficiency is improved, pollution emissions and energy consumption are reduced, the requirements on green chemical process are met, and the method is suitable for industrialized production.

Antitumor drugs and preparation method and application thereof

The invention relates to antitumor drugs and a preparation method and application thereof, in particular to a compound shown as a following formula (I). The compound adopts Cu-Kalpha radiation and hasa typical powder X-ray diffraction pattern shown in a figure 1. The invention also provides a preparation method of the compound, a pharmaceutical composition comprising the compound and the application of the compound in preparation of the drugs for resisting tumors such as, but not limited to, colon cancer, lymphoma, sarcoma, leukemia, pancreatic cancer, breast cancer, prostate cancer, bone cancer, liver cancer, kidney cancer, lung cancer, testicular cancer, skin cancer, stomach cancer, colorectal cancer, renal cell carcinoma, hepatocellular carcinoma and melanoma. The compound has excellent performance.