314771-88-5

Usage

Uses

Used in Pharmaceutical Synthesis:
4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]is used as a key intermediate in the synthetic preparation of 4-anilinoquinazolines with C-6 urea-linked side chains. These synthesized compounds serve as inhibitors of the epidermal growth factor receptor (EGFR), which is a common target for cancer therapies. By inhibiting EGFR, these agents can help control the growth and proliferation of cancer cells.
Used in Oncology:
In the field of oncology, 4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]is utilized in the preparation of (2Z)-Afatinib (A355305), a potent EGFR inhibitor. Afatinib is used for treating various types of cancer, including those of the respiratory tract, lungs, gastrointestinal tract, bile duct, and gallbladder. By targeting the EGFR pathway, Afatinib can help slow down or stop the growth of cancer cells, providing a valuable treatment option for patients with these conditions.
Used in Respiratory Disease Treatment:
4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]also plays a role in the development of treatments for respiratory diseases. 4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]is involved in the synthesis of (2Z)-Afatinib, which has been found to be effective in managing conditions such as asthma and chronic obstructive pulmonary disease (COPD). By targeting the EGFR pathway, Afatinib can help reduce inflammation and improve lung function in patients with these respiratory disorders.

Upstream product

• 945553-94-6 N-((3-chloro-4-fluorophenyl)-6-nitro-7-phenylsulfonyl)quinazolin-4-one 
• 86087-23-2 (S)-3-hydroxytetyrahydrofurane 
• 367-21-5 3-chloro-4-fluorophenylamine 
• 162012-67-1 N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine 
• 162012-70-6 4-chloro-7-fluoro-6-nitroquinazoline 
• 31374-18-2 7-chloro-3,4-dihydroquinazolin-4-one 
• 53449-14-2 7-chloro-6-nitro-4(3H)-quinazolinone 
• 162012-71-7 4,7-dichloro-6-nitro-quinazoline 
• 446-32-2 4-fluoroanthranilic acid 
• 16499-57-3 7-fluoro-3,4-dihydroquinazolin-4-one 
• 162012-69-3 7-fluoro-6-nitro-4-hydroxyquinazoline 
• 602261-99-4 2-chloro-1-fluoro-4-isocyanobenzene 
• 27684-84-0 5-bromo-2-nitrophenol 
• 770-22-9 N-(3-chloro-4-fluoro-phenyl)-formamide 

Downstream Products

• 314771-76-1 6-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline 
• 1613293-54-1 C₂₁H₁₈ClFN₄O₅S 
• 1613293-56-3 C₁₈H₁₅ClFN₃O₂S 
• 1613293-57-4 C₁₉H₁₇ClFN₃O₂ 
• 1613293-58-5 C₁₉H₁₆BrClFN₃O₂ 
• 1613293-50-7 C₂₃H₂₀ClFN₄O₄ 
• 1613293-49-4 C₂₀H₁₆ClFN₄O₄S 
• 1613293-53-0 C₂₄H₂₁ClFN₅O₅ 
• 1420404-08-5 (Z)-(S)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-2-fluoro-4-morpholinobut-2-enamide 
• 1420404-12-1 (E)-(S)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-2-fluoro-4-morpholinobut-2-enamide 
• 1420404-16-5 (Z)-(S)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)-2-fluorobut-2-enamide 
• 1420404-20-1 (E)-(S)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)-2-fluorobut-2-enamide 

Relevant academic research and scientific papers

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.

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.

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.

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:

4 - (Substituted phenylamino) aminoquin oxazolines, preparation method and application thereof

The invention specifically relates to novel 4-(substituted phenylamino)quinazoline compounds with antineoplastic activity and a preparation method thereof, belonging to the field of pharmaceutical chemical engineering. The 4-(substituted phenylamino)quinazoline compounds have an effective irreversible inhibiting effect on tyrosine kinase and/or good in-vivo pharmacokinetic behavior and are an effective tyrosine kinase irreversible inhibitor.

Design, synthesis, and docking studies of quinazoline analogues bearing aryl semicarbazone scaffolds as potent EGFR inhibitors

Two series of quinazoline derivatives bearing aryl semicarbazone scaffolds (9a–o and 10a–o) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF-7 and PC-3). The selected compound 9o was further evaluated for the inhibitory activity against EGFR kinases. Four of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 values in single-digit μM to nanomole range. Two of them are equal to more active than positive control afatinib against one or more cell lines. The most promising compound 9o showed the best activity against A549, HepG2, MCF-7 and PC-3 cancer cell lines and EGFR kinase, with the IC50 values of 1.32?±?0.38?μM, 0.07?±?0.01?μM, 0.91?±?0.29?μM and 4.89?±?0.69?μM, which were equal to more active than afatinib (1.40?±?0.83?μM, 1.33?±?1.28?μM, 2.63?±?1.06?μM and 3.96?±?0.59?μM), respectively. Activity of the most promising compound 9o (IC50 56?nM) against EGFR kinase was slightly lower to the positive compound afatinib (IC50 1.6?nM) but more active than reference staurosporine (IC50 238?nM). The result of flow cytometry, with the dose of compound 9o increasing, which indicated the compound 9o could induce remarkable apoptosis of A549 and cells in a dose dependent manner. Structure–activity relationships (SARs) and docking studies indicated that replacement of the cinnamamide group by aryl semicarbazone scaffolds slightly decreased the anti-tumor activity. The results suggested that hydroxy substitution at C-4 had a significant impact on the activity and replacement of the tetrahydrofuran group by methyl moiety was not beneficial for the activity.

Quinazoline compound containing acylhydrazone structure and application thereof

The invention discloses a quinazoline compound containing an acylhydrazone structure. The quinazoline compound is as shown in a formula I in the description. The invention relates to the quinazoline compound comprising the acylhydrazone structure, a pharmaceutically acceptable salt, a hydrate or a solvate as active ingredients, and the active ingredients are mixed with a pharmaceutically acceptable carrier or an excipient to prepare a composition and prepare a clinically acceptable dosage. The compound disclosed by the invention can treat and/or prevent proliferative diseases and prostatic cancer, lung cancer and cervical cancer.

Improving method of afatinib synthesis technology

The invention discloses an improving method of an afatinib synthesis technology, and belongs to the technical field of organic synthesis. Chlorination, amination, etherification and reduction reactions in the afatinib synthesis technology are improved and optimized, so the method improves the yield and the purity of a product, simplifies technology operation, reduces the production cost, realizes convenient and clean post-treatment, and has high practicality. Compared with the prior art, the improving method of the afatinib preparation technology overcomes many shortages, has a high yield, has simple steps, and allows the total yield to be about 71% and the purity to be 98%. The method has the main advantages of simplified steps, mild reaction conditions, simplicity in operation, high yield, high purity, and facilitation of industrial production.

Compound, and preparation method and application thereof

The invention relates to a compound, and a preparation method and application thereof. Specifically, the compound is as shown in a formula 1 which is described in the specification. The invention also provides the preparation method for the compound as shown in the formula 1. The preparation method comprises a step of contacting N-[4-[(3-chloro-4-fluorophenyl)amino]-7[[(3S)-tetrahydro-3-furyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-2-butyleneamide with an alkaline aqueous solution in an organic solvent so as to obtain the compound as shown in the formula 1. The preparation method is simple to operate; a white powder product can be obtained through direct filtering after post-treatment; and the prepared compound has high purity, as high as 99% or above, and can be directly used as an impurity control substance for research on the quality of an afatinib bulk drug.

Method for preparing intermediate of Afatinib

The invention discloses a method for preparing an intermediate of Afatinib. The method comprises the following step: subjecting a compound represented by a formula 7 shown in the description, sodium methanesulfonate and (S)-3-hydroxyl tetrahydrofuran to a reaction as follows in an organic solvent in the presence of alkali, thereby preparing a compound represented by a formula 9 shown in the description. The method disclosed by the invention is high in yield, simple in operation and low in cost and is more applicable to industrial production.