Synthesis of 2-(4-Isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-ol; A Quinoline Building Block for Simeprevir Synthesis

Rádl, S.; Rezková, Hana; Obadalová, Iva; Srbek, Jan; Břicháč, Jiří; Pekárek, Tomáš

doi:10.1055/s-0033-1340679

Cited by 4 publications

(2 citation statements)

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“…In our choice of groups at C4, we were conscious that a quinoline to quinolone transformation would be very valuable as this methodology could provide an excellent route to substituted fluoroquinolones. We anticipated that compounds 2a , 2b , 2d , and 2e could undergo acid-hydrolysis to provide the corresponding 4-quinolone, 15 while orthogonally, 2c could be deprotected using palladium-catalyzed hydrogenation ( vide infra ). 16 …”

Section: Resultsmentioning

confidence: 99%

Iridium-Catalyzed Borylation of 6-Fluoroquinolines: Access to 6-Fluoroquinolones

et al. 2022

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Section: Resultsmentioning

confidence: 99%

Iridium-Catalyzed Borylation of 6-Fluoroquinolines: Access to 6-Fluoroquinolones

et al. 2022

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“…Acylation of aniline 142 with 4‐isopropylthiazole‐2‐carbonyl chloride provided amidoacetophenone 143 , which was cyclised using tert‐ BuOK at 100 °C to complete the synthesis of 144 . Alternative routes to 144 that provided improved yields, and that did not require chromatographic purification have also been reported …”

Section: Major Classes Of Bro5 Drugs—background and Synthesismentioning

confidence: 99%

Drug Syntheses Beyond the Rule of 5

Tyagi

Begnini

Poongavanam

et al. 2019

Chemistry A European J

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Drugs in the chemical space beyond the rule of 5 (bRo5) can modulate targets with difficult binding sites while retaining cell permeability and oral absorption. Reviewing the syntheses of bRo5 drugs approved since 1990 highlights synthetic chemistry's contribution to drug discovery in this space. Initially, bRo5 drugs were mainly natural products and semi‐synthetic derivatives. Later, peptidomimetics and de novo designed compounds, that include up to seven chiral centres and macrocyclic rings became dominant. These drugs are prepared by total synthesis, sometimes by routes of more than 25 steps with stereocentres originating from the chiral pool, or being installed by chiral induction or enzymatic resolution. Interestingly, ring‐closing metathesis proved to be the method of choice for macrocyclisation in hepatitis C virus protease inhibitors. We conclude that structural simplification, planning of synthetic routes regarding incorporation of stereocentres and macrocyclisation, as well as incorporation of structural knowledge and consideration of chameleonic properties in design, should facilitate drug discovery in bRo5 space.

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ChemInform Abstract: Synthesis of 2‐(4‐Isopropylthiazol‐2‐yl)‐7‐methoxy‐8‐methylquinolin‐4‐ol; a Quinoline Building Block for Simeprevir Synthesis.

et al. 2014

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Synthesis. -Two different approaches to the title compound which is a building block of the drug candidate simeprevir with specific HCV protease inhibitory activity are described. Both syntheses proceed via methyl 4,7-dimethoxy-8-methylquinoline-2-carboxylate the preparation of which from the corresponding aniline is elaborated. -(RADL*, S.; REZKOVA, H.; OBADALOVA, I.; SRBEK, J.; BRICHAC, J.; PEKAREK, T.; Synthesis 46 (2014) 7, 899-908, http://dx.

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Synthesis of 2-(4-Isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-ol; A Quinoline Building Block for Simeprevir Synthesis

Cited by 4 publications

References 2 publications

Iridium-Catalyzed Borylation of 6-Fluoroquinolines: Access to 6-Fluoroquinolones

Iridium-Catalyzed Borylation of 6-Fluoroquinolines: Access to 6-Fluoroquinolones

Drug Syntheses Beyond the Rule of 5

ChemInform Abstract: Synthesis of 2‐(4‐Isopropylthiazol‐2‐yl)‐7‐methoxy‐8‐methylquinolin‐4‐ol; a Quinoline Building Block for Simeprevir Synthesis.

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