A Different Approach to the EGFR Inhibitor Gefitinib Involving Solid-Phase Synthesis

Sequeira, André; Lourenço, Ana; Ferreira, Luı́sa M.; Branco, Paula S.; Mendes, Zita; Lourenço, Nuno M. T.; Figueiredo, Mauro; Carvalho, Luísa C. R.

doi:10.1055/s-0037-1610127

Cited by 4 publications

(1 citation statement)

References 29 publications

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“…As an intermediate common to Gefitinib and Larotinib, the use of hydroxyquinazoline 6 is instrumental for the economic and procedural advantages of route I , and its higher overall yield. Compared the various conditions reported for route I , several representative conditions are listed in Table , which summarizes their advantages and disadvantages for the synthesis of 6 .…”

Section: Introductionmentioning

confidence: 99%

Continuous Flow Synthesis of a Key Intermediate Common to Gefitinib and Larotinib

Zhang,

Li,

et al. 2024

Org. Process Res. Dev.

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Herein, we demonstrate a continuous flow synthesis method for 4-(3-chloro-4-fluorophenylamino)-6-hydroxy-7methoxyquinazoline, a key intermediate of Gefitinib and Larotinib. The process comprises three chemical transformations, chlorination, amination, and hydrolysis, in three sequential continuous flow devices. First, a single-step continuous flow chlorination is demonstrated in an agitated tube reactor with a yield of 92.7% and a residence time of 10 min. Second, the combined continuous flow chlorination and amination are demonstrated in 96.1% yield with a residence time of 12.5 min. Finally, continuous flow synthesis of the target compound is demonstrated in 85.1% total yield with a total residence time of 18.5 min.

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Section: Introductionmentioning

confidence: 99%

Continuous Flow Synthesis of a Key Intermediate Common to Gefitinib and Larotinib

Zhang,

Li,

et al. 2024

Org. Process Res. Dev.

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Design and development of folic acid engineered magnetic graphene oxide nanosheets for selective synergistic chemophotothermal inhibition of lung cancer cell

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Bangde,

Pandey

et al. 2024

Journal of Drug Delivery Science and Technology

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Flow Photocleavage for Automated Glycan Assembly (AGA)

Teschers

Gilmour

2020

Org. Process Res. Dev.

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Automated glycan assembly (AGA) is contingent on the development of simple, efficient cleavage strategies to liberate complex, high value products from a solid support resin. Given the rapid advances in the structural complexity of carbohydrates that can be constructed via this enabling technology, effective cleavage is a persistent challenge. Photolabile linkers have a venerable history in AGA and mitigate potential complications arising from chemically induced release protocols. However, photochemical cleavage strategies have traditionally relied upon mercury vapor lamps, which present challenges in establishing welldefined, reproducible, and nonhazardous conditions for this ultimate step of the AGA sequence. To complement the existing batch strategies, a safe and sustainable approach for the continuous flow photocleavage from solid support using LEDs has been developed. By employing a custom-built LED flow reactor, photocleavage yields of up to 80% were achieved in less than 1 h. Efficiency could be further improved by merging flow photochemistry with pregrinding. Validation of this strategy is showcased in a proof of concept AGA synthesis of a model dimannoside.

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A Different Approach to the EGFR Inhibitor Gefitinib Involving Solid-Phase Synthesis

Cited by 4 publications

References 29 publications

Continuous Flow Synthesis of a Key Intermediate Common to Gefitinib and Larotinib

Continuous Flow Synthesis of a Key Intermediate Common to Gefitinib and Larotinib

Design and development of folic acid engineered magnetic graphene oxide nanosheets for selective synergistic chemophotothermal inhibition of lung cancer cell

Flow Photocleavage for Automated Glycan Assembly (AGA)

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