314771-76-1

Basic information

• Product Name: (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine
• Synonyms: 4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-amine-7-[[(3S)-tetrahydro-3-furanyl]oxy]-;4,6-Quinazolinediamine, N4-(3-chloro-4-fluorophenyl)-7-[[(3S)-tetrahydro-3-furanyl]oxy]-;Afatinib-des(4-dimethylamino-2-en-1-oxo)butyl;Intermediates of sunitinib;(S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine;N4-(3-Chloro-4-fluorophenyl)-7-[[(3S)-tetrahydro-3-furanyl]oxy]-4,6-quinazolinediamine;7-((S)-tetrahydrofuran-3-yloxy)-4-(3-chloro-4-fluorophenyl) aMino-6-aMinoquinazoline;Afatinib IMpurity B
• CAS NO: 314771-76-1
• Molecular Formula: C18H16ClFN4O2
• Molecular Weight: 374.7966432
• EINECS: 1312995-182-4
• Product Categories: Afatinib Dimaleate
• Mol File: 314771-76-1.mol

Chemical Properties

• Boiling Point: 559.0±50.0 °C(Predicted)
• Appearance: /
• Density: 1.473±0.06 g/cm3 (20 ºC 760 Torr)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 5.89±0.30(Predicted)
• CAS DataBase Reference: (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine(314771-76-1)
• EPA Substance Registry System: (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine(314771-76-1)

Safety Data

• Hazardous Substances Data: 314771-76-1(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
(S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diamine is used as an organic synthesis intermediate for the preparation of a range of chemical compounds. Its unique structure allows it to be a key component in the synthesis of complex organic molecules, which can be used in various applications, such as the development of new materials or the creation of novel chemical entities.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diamine is used as a pharmaceutical intermediate. It plays a crucial role in the development of new drugs, as its molecular structure can be modified to create potential therapeutic agents. (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diamine can be a precursor to various pharmaceuticals, contributing to the advancement of medicine and the treatment of various diseases.
Used in Laboratory Research and Development:
(S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diamine is also utilized in laboratory research and development processes. Researchers use this compound to explore its chemical properties, reactivity, and potential applications in various fields. It can be a valuable tool for understanding the fundamental aspects of organic chemistry and for developing new synthetic methods and techniques.
Used in Chemical Production Process:
Finally, (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diamine is employed in the chemical production process. It can be a key ingredient in the manufacturing of various chemical products, contributing to the efficiency and effectiveness of industrial chemical processes. Its use in this context highlights the importance of this compound in the broader chemical industry.

Synthesis

To a solution of 4-(3-chloro-4-fluorophenyl)amino-6-nitro-7-[[(S)-tetrahydro-3-furanyl]oxy]- quinazoline (1.34 g, 3.31 mmol) and ammonium chloride (496 mg, 9.27 mmol) in anhydrous DMF (22 mL), Raney nickel [1.5 mL, 50 % (w/v) in water] was added to the reaction mixture and stirred under an atmosphere of hydrogen at 40 °C for 2 h. After 2 h the reaction was diluted with EtOH (10 mL), filtered through diatomaceous earth and washed with a large excess of EtOH. The residue was concentrated under reduced pressure and purified by column chromatography eluting with CHCl3/MeOH (95:5) to give 6 as a viscous brown oil (950 mg, 77 %).

Upstream product

• 314771-88-5 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline 
• 367-21-5 3-chloro-4-fluorophenylamine 
• 162012-70-6 4-chloro-7-fluoro-6-nitroquinazoline 
• 162012-67-1 N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine 
• 1621182-18-0 6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]-3,4-dihydroquinazoline-4-one 
• 314771-88-5 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-[(R)-(tetrahydrofuran-3-yl)oxy]quinazoline 
• 60-29-7 diethyl ether 
• 7439-89-6 iron 
• 850140-73-7 [N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4(dimethylamino)-2-butenamide] dimaleate 
• 314771-88-5 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-(5-tetrahydrofuran-3-yloxy)quinazoline 
• 770-22-9 N-(3-chloro-4-fluoro-phenyl)-formamide 
• 27684-84-0 5-bromo-2-nitrophenol 
• 602261-99-4 2-chloro-1-fluoro-4-isocyanobenzene 
• 16499-57-3 7-fluoro-3H-quinazolin-4-one 

Downstream Products

• 1613293-56-3 C₁₈H₁₅ClFN₃O₂S 
• 1613293-58-5 C₁₉H₁₆BrClFN₃O₂ 
• 1613293-50-7 C₂₃H₂₀ClFN₄O₄ 
• 1613293-49-4 C₂₀H₁₆ClFN₄O₄S 
• 1613293-57-4 C₁₉H₁₇ClFN₃O₂ 
• 1613293-53-0 C₂₄H₂₁ClFN₅O₅ 

Relevant articles and documents

Isolation and structural characterization of degradation products of afatinib dimaleate by LC-Q-TOF/MS/MS and NMR: cytotoxicity evaluation of afatinib and isolated degradation products

Afatinib is an irreversible tyrosine kinase receptor inhibitor which was approved lately by USFDA for the treatment of metastatic non-small cell lung cancer (NSCLC). AFT was subjected to stress degradation studies under hydrolytic (acid, base and neutral), oxidative, thermal and photolytic conditions to investigate the inherent stability of the drug. The present study describes the simple and rapid HPLC method development for the selective separation of the AFT and its degradation products. The drug and degradation products were separated on Agilent Eclipse plus C18 (150 × 4.6 mm, 5 μ) column with ammonium acetate buffer (10 mM, pH 6.7) in gradient elution mode. The drug was found to be unstable in all the conditions studied. The developed chromatographic method was extended to tandem mass spectrometry (QTOF-MS) for the characterization of the degradation products. A total of 11 unknown degradation products were characterized using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS/MS). Two major degradation products (DP2 and DP3) were isolated using preparative HPLC and their structures were confirmed by conducting 1H and 13C NMR experiments. The isolated DPs were evaluated for their anticancer potential using non small cell lung cancer cell line A549. The IC50 values for AFT, DP2 and DP3 were found to be 15.02 ± 1.49, 25.00 ± 1.26 and 32.56 ± 0.11 respectively. The in silico toxicity studies were performed employing ProTox-II software for the assessment of toxicity potential of drug and its degradation products. Finally, the developed chromatographic method was validated as per the International Conference on Harmonization guideline Q2 (R1).

Industrial Cunninghamia lanceolata carbon supported FeO(OH) nanoparticles-catalyzed hydrogenation of nitroarenes

The development of green and efficient methods for hydrogenation of nitroarenes is still highly demanding in organic synthesis. Herein, we report an industrial Cunninghamia lanceolata carbon supported FeO(OH) nanoparticles process for the synthesis of aryl amines with good yields via hydrogenation of nitroarenes. Nine key anti-cancer drug intermediates were successfully achieved with protocol. And Osimertinib intermediate 4m can be smoothly synthesized at a 2.67 kg-scale with >99.5% HPLC purity. This protocol features cheap carbon source, highly catalytic activity, simple operation, kilogram-scalable and recyclable catalysts (eight times without observable losing activity).

Preparation method of afatinib intermediate

The invention discloses an afatinib intermediate preparation method, which comprises: (1) adding a compound represented by a formula II, sodium thiosulfate, sodium bicarbonate and N, N-dimethylformamide into a reaction device, heating, completely reacting

Synthetic method of afatinib intermediate

The invention discloses a synthesis method of an afatinib intermediate, which comprises the following steps: adopting a compound (I), by using hydrazine hydrate as a reducing agent, FeCl3. 6H2O as a catalyst, activated carbon as a carrier and a THF/MeOH s

Preparation method and application of aniline quinazoline intermediate

The invention discloses a preparation method and application of an aniline quinazoline intermediate. The preparation method comprises the following steps: with N-(3-chloro-4-fluorophenyl)-7-[(S)-tetrahydro-3-furyl-oxy]-6-nitro-4-quinazolinamine as a raw m

Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers

A series of quinazoline derivatives with benzylidene hydrazine carboxamide were designed and synthesised as EGFR inhibitors. Most compounds exhibited exceptional anti-proliferative activity against A549, HepG2, MCF-7 and H1975 cells. Furthermore, six compounds demonstrated excellent inhibition activity against EGFRWT with the IC50 value both less than 2 nM. Among the six compounds, 44 exhibited the strongest activity (0.4 nM) and potently inhibited EGFRL858R/T790M (0.1 μM). Excitingly, the most potent compound 14 showed excellent enzyme inhibitory activity with 6.3 nM and 8.4 nM for both EGFRWT and EGFRT790M/L858R. The result of AO single staining and Annexin V/PI staining showed that the compound 14 and 44 could induce remarkable apoptosis of A549 cells. The compound 14 arrested the cell cycle at the S phase and compound 44 arrested the cell cycle at the G0 phase in A549 cells. These preliminary results demonstrate that compound 14 and 44 may be promising lead compound-targeting EGFR.

Arab league law for nepal intermediate high purity preparation method

The present invention relates to a high purity preparation method of Afatinib intermediate, and particularly relates to a high purity preparation method of an antineoplastic treatment medicine maleate Afatinib intermediate (II) compound, the method comprises the following steps: an objective product is obtained sequentially through substitution in two steps, reduction reaction and the like of 6-amino-7-fluoro-3,4-dihydro-quinazolin-4-one. The method is simple in process, economic and environmental-friendly, and suitable for industrial amplification requirements, and the manufactured finished product is high in purity.

Afatinib refined product synthetic method

The invention discloses an afatinib refined product synthetic method, and belongs to the technical field of organic synthesis. The method particularly comprises the following steps that 4-fluoro-2-aminobenzoic acid and formamidine acetate are subjected to a ring-closure reaction to synthesize a compound of the formula I; the compound of the formula I is subjected to a nitration reaction to synthesize a compound of the formul II; the compound of the formula II and 3-chloro-4-fluoroaniline are subjected to dehydration to synthesize a compound of the formula III, the compound of the formula III and 3-hydroxy-tetrahydrofuran synthesize a compound of a formula IV through a nucleophilic substitution reaction; the compound of the formula IV is reduced to generate a compound of the formula V underthe Pd/C catalysis; the compound of the formula V and crotonic acid synthesizes a compound of the formula VI through a dehydration condensation reaction; the compound of the formula VI and dimethylamine finally synthesize the compound of the formula VII, that is to say, an afatinib refined product is obtained. According to the afatinib refined product synthetic method, the reaction process condition is mild, the corrosion risk to reaction equipment is lowered, the reaction process is simplified, operation is easy, the purity of the product is high, and the yield is increased conveniently.

PROCESS FOR THE PREPARATION OF N-[4-[(3-CHLORO-4-FLUORO PHENYL) AMINO]-7-[[(3s-TETRAHYDRO-3-FURANYL]OXY]-6-QUINAZOLINYL]-4-(DIMETHYL AMINO)-(2E)-2-BUTENAMIDE (2Z)-2-BUTENEDIOATE (1 :2) AND ITS POLYMORPHS THEREOF

The present invention relates to an improved process for the preparation of N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethyl amino)-(2E)-2-butenamide (2Z)-2-butenedioate (1:2) represented by the following structural formula:

A preparation method of the midbody arab league law for nepal

The invention provides a preparation method of an Afatinib intermediate and particularly provides a preparation method of N-(3-chloro-4- fluorophenyl)-7-[[(3S)-tetrahydro-3-furyl]oxy]-4,6-quinazoline diamine. According to the method, 4-[(3-chloro-4-flu