1075705-01-9

Basic information

• Product Name: 4-fluoro-2-Methoxy-5-nitroaniline
• Synonyms: 4-fluoro-2-Methoxy-5-nitroaniline;2-Amino-5-fluoro-4-nitroanisole, 4-Fluoro-5-nitro-o-anisidine;4-Fluoro-2-Methoxy-5-nitrobenzenaMine;Benzenamine, 4-fluoro-2-methoxy-5-nitro-;4-fluoro-2-methoxy-5-nitrophenylamine
• CAS NO: 1075705-01-9
• Molecular Formula: C₇H₇FN₂O₃
• Molecular Weight: 186.1404832
• EINECS: 1592732-453-0
• Product Categories: AZD9291
• Mol File: 1075705-01-9.mol
• Article Data: 41

Chemical Properties

• Melting Point: 130 °C
• Boiling Point: 354.8±37.0 °C(Predicted)
• Appearance: /
• Density: 1.412±0.06 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 2.31±0.10(Predicted)
• CAS DataBase Reference: 4-fluoro-2-Methoxy-5-nitroaniline(CAS DataBase Reference)
• NIST Chemistry Reference: 4-fluoro-2-Methoxy-5-nitroaniline(1075705-01-9)
• EPA Substance Registry System: 4-fluoro-2-Methoxy-5-nitroaniline(1075705-01-9)

Safety Data

• Hazardous Substances Data: 1075705-01-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-fluoro-2-Methoxy-5-nitroaniline is used as a reagent for the synthesis of anticancer drugs, specifically in the preparation of Mereletinib. Mereletinib is a potent and selective inhibitor of the fibroblast growth factor receptor (FGFR) family, which plays a crucial role in various types of cancer cell growth and survival. By targeting FGFR, Mereletinib can effectively inhibit tumor growth and progression, making it a valuable therapeutic option for cancer patients.
In addition to its use in the synthesis of Mereletinib, 4-fluoro-2-Methoxy-5-nitroaniline may also have potential applications in the development of other pharmaceutical compounds due to its unique chemical properties. Its ability to form various functional groups and interact with different molecular targets makes it a promising candidate for further research and development in the pharmaceutical field.

Synthesis

4-FLUORO-2-METHOXYANILINE(551 mg, 3.90 mmol) is dissolved in dichloromethane (39.0 mL), concentrated sulfuric acid (1.85 mL) is added dropwise with stirring under ice-cooling, and then concentrated nitric acid (267 μL, 5.85 mmol) is added dropwise. After stirring for 3 hours under ice-cooling, saturated aqueous sodium bicarbonate was added until pH 8 was reached. After washing with saturated aqueous sodium bicarbonate solution, washing with saturated brine, the organic layer was dried over sodium sulfate and evaporated under reduced pressure to obtain 675 mg of the 4-fluoro-2-Methoxy-5-nitroaniline (yield 93%).

Upstream product

• 124-41-4 sodium methylate 
• 123344-02-5 5-amino-2,4-difluoronitrobenzene 
• 367-25-9 2,4-difluorophenylamine 
• 394-18-3 1-fluoro-5-methoxy-2,4-dinitrobenzene 
• 582-11-6 N-(4-fluoro-2-methoxyphenyl)acetamide 
• 446-36-6 5-fluoro-2-nitrophenol 
• 446-35-5 2,4-Difluoronitrobenzene 
• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 
• 450-91-9 4-fluoro-2-methoxyaniline 

Downstream Products

• 1407520-43-7 C₂₆H₃₃ClN₇O₅P 
• 1407520-44-8 C₂₆H₃₅ClN₇O₃P 
• 1407520-49-3 C₂₃H₂₉ClN₇O₄P 
• 1407520-42-6 (2-((5-chloro-2-((4-fluoro-2-methoxy-5-nitrophenyl)amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide 

Relevant articles and documents

Optimization and Scale-Up of the Continuous Flow Acetylation and Nitration of 4-Fluoro-2-methoxyaniline to Prepare a Key Building Block of Osimertinib

The development of a scalable telescoped continuous flow procedure for the acetylation and nitration of 4-fluoro-2-methoxyaniline is described. A subsequent batch deprotection then affords 4-fluoro-2-methoxy-5-nitroaniline, a key building block in the synthesis of osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is used for the treatment of nonsmall-cell lung carcinomas carrying EGFR-TKI sensitizing and EGFR T790M resistance mutations. The hazards associated with nitration of organic compounds, such as thermal runaway and explosivity of intermediates, make it difficult to scale up nitrations to industrial quantities, particularly within large-scale batch reactors. In this study, we investigated an acetic acid/aqueous nitric acid mixture as a predominantly kinetically controlled nitration regime and a water-free mixture of acetic acid, fuming nitric acid, and fuming sulfuric acid (oleum) as a mass-transfer-limited nitration regime. A modular microreactor platform with in-line temperature measurement was utilized for the nitration. Furthermore, we identified that it was necessary to protect the amine functionality through acetylation to avoid side reactions. The process parameters and equipment configuration were optimized at laboratory scale for the acetylation and nitration to improve the product yield and purity. The two steps could be successfully telescoped, and the laboratory-scale flow process was operated for 80 min to afford the target molecule in 82% isolated yield over two steps, corresponding to a throughput of 25 mmol/h. The developed flow process was then transferred to an industrial partner for commercial implementation and scaled up by the use of higher flow rates and sizing-up of the microreactor platform to pilot scale to afford the product in 83% isolated yield, corresponding to a throughput of 2 mol/h (0.46 kg/h).

New and Convergent Synthesis of Osimertinib

New and convergent synthetic route of osimertinib is described on a dozen of grams scale. A key cyclization of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)guanidine and 3-(dimethylamino)-1-(1-methyl-1H-indol-3-yl)prop-2-en-1-one is adopted to give the 4-(1H-indol-3-yl)-N-phenylpyrimidin-2-amine structure. Osimertinib is prepared in 40.4% yield over six steps and 99.1% purity (HPLC). Purification methods of the intermediates involved in the route are also given.

Synthesis method of osimertinib intermediate

The invention relates to a synthesis method of an osimertinib intermediate. The synthesis method comprises the following steps: 1, with 3-fluoroanisole as an initial raw material, adding 3-fluoroanisole into concentrated sulfuric acid, dropwise adding the concentrated nitric acid in a low-temperature environment, carrying out primary heating and stirring after completion of the addition, injectingthe formed system into ice water for quenching, carrying out secondary heating and stirring, and carrying out filtering to obtain a product, namely 3-fluoro-4, 6-dinitroanisole; and 2, adding the compound 3-fluoro-4,6-dinitroanisole obtained in the step 1 into water, adding alkali, conducting heating, adding a weak reducing agent in batches, performing stirring while keeping the temperature untila reaction endpoint is reached, carrying out filtering to obtain a crude product, and successively conducting washing, recrystallizing with methanol, crystallizing and filtering at a low temperatureand drying to finally obtain 4-fluoro-2-methoxy-5-nitroaniline. The method of the invention solves the problems that raw materials are expensive and hardly-available in the market, process is complexand yield is low in conventional synthesis methods of the osimertinib intermediate.

Compound for inhibiting three-mutant epidermal growth factor receptor tyrosine kinase and application thereof

The invention discloses a compound for inhibiting three-mutant epidermal growth factor receptor tyrosine kinase, and is characterized in that the structural formula is as follows. Among them: Substituent R1 . One of: Substituent R2 . One of: The substituent X is H or Cl. Substituent R3 To H. One of the following.

BENZIMIDAZOLE DERIVATIVES

The invention relates to benzimidazoles of Formula (I) and pharmaceutically acceptable salts thereof, wherein R1 to R6 are as defined in the description; to their use in medicine; to compositions containing them; to processes for their preparation; and to intermediates used in such processes. The benzimidazoles of Formula (I) are ITK inhibitors and are therefore potentially useful in the treatment of a wide range of disorders including, atopic dermatitis.

Improvements in the Synthesis of the Third-Generation EGFR Inhibitor Osimertinib

Osimertinib, a third generation potent and specific EGFR inhibitor is an important drug against many forms of cancer. It was synthesized by an improved and highly efficient protocol, revisiting the classical synthetic process and modifying parameters, such as solvents, temperature, reagents, and reaction time. A cost-effective, environmentally friendly methodology for the synthesis of osimertinib was established, which gave shorter reaction times, saved labor by eliminating purification steps through column chromatography, and enhanced yields. Four of the seven steps in total, were proceeded quantitatively or almost quantitatively (ca. 98 %). This synthetic protocol provides a very high overall yield, up to 68 %. In addition, the entire approach enables the preparation of osimertinib analogues and could be extended in the synthesis of other structurally similar bioactive compounds.

Novel crystal form of deuterated AZD9291 compound and application thereof (by machine translation)

The invention belongs to the technical field of medicines, and particularly discloses a preparation method AZD9291 of a novel crystal form, and of deuterated . and application AZD9291 of the deuterated, crystal form is stable in crystal form, crystal form stability compared with crystal form DVS by combining suspension experiment with acceleration stability study, at normal temperature and accelerated stability. AZD9291. The present invention further discloses the crystal form A of a deuterated C . crystal form. (by machine translation)

The therapeutic effect of the anticancer agent for predicting alternative (by machine translation)

[Problem] non-small cell lung cells resistant to various epidermal growth factor receptor gene mutation appears when, for selecting alternative anticancer effects, minimally invasive or non-invasive diagnosis of a genetic therapeutic effect of anticancer agent can be labeled with radioactive alternative predicted. The therapeutic effect of the anticancer agent is predicted [solution] alternatively, the anticancer drug is selected to be labeled with a radioactive isotope which alternate, the anticancer drug resistance should be selected to be an alternative to the anticancer agent is preferably labeled with a radioactive isotope as an alternative. The therapeutic effect of the anticancer agent is an alternative prediction, wherein the anticancer agent is an anticancer agent are alternative, epidermal growth factor receptor due to genetic drug resistance, epidermal growth factor receptor tyrosine kinase inhibitors is that. [Drawing] no (by machine translation)

Purine compounds and application thereof

The invention relates to purine derivatives represented as the general formula I and pharmaceutically acceptable salts, hydrates or prodrugs of the purine derivatives. Substituent groups X, R1, R1', R2, R3, R4 and Ar have the meaning given in the description. The invention further relates to a function of the compounds represented as the general formula I in inhibition of EGFR (epidermal growth factor receptor) kinase and mutants of EGFR kinase, in particular to an application of the compounds and the pharmaceutically acceptable salts, hydrates or prodrugs thereof to preparation of drugs for treating diseases related to EGFR kinase activity, especially an application to preparation of drugs for treating and/or preventing cancer.

2-(2, 4, 5-substituted aniline) pyrimidine derivative

The invention relates to a 2-(2, 4, 5-substituted aniline) pyrimidine derivative, and more specifically discloses a compound represented by formula I or a pharmaceutically acceptable salt thereof, anda preparation method and applications of the compound represented by formula I and the pharmaceutically acceptable salt of the compound, wherein R1 to R9 are used for representing groups defined in the invention.