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Ripretinib

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CAS:1442472-39-0
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CAS:1442472-39-0
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CAS: 1442472-39-0
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CAS:1442472-39-0
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  • CAS:1442472-39-0
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Related articles

  • Synthesis of Ripretinib
  • Ripretinib was synthesized by construction of a 1,6-naphtholide involving the junction of an α-aryl ester and appropriately fu....
  • Jan 2,2024
Ripretinib Basic information
Product Name:Ripretinib
Synonyms:KIT/PDGFR inhibitor(DCC2618);KIT/PDGFR INHIBITOR(DCC-2618);Ripretinib;Ripretinib (DCC-2618);DCC-2618; DCC 2618; DCC2618; RIPRETINIB;;DCC-2618;KIT/PDGFR INHIBITOR;KIT/PDGFR inhibitor;N-[4-Bromo-5-[1-ethyl-1,2-dihydro-7-(methylamino)-2-oxo-1,6-naphthyridin-3-yl]-2-fluorophenyl]-N'-phenylurea
CAS:1442472-39-0
MF:C24H21BrFN5O2
MW:510.36
EINECS:
Product Categories:API
Mol File:1442472-39-0.mol
Ripretinib Structure
Ripretinib Chemical Properties
Boiling point 568.6±50.0 °C(Predicted)
density 1.544±0.06 g/cm3(Predicted)
storage temp. Store at -20°C
solubility DMSO:25.0(Max Conc. mg/mL);49.0(Max Conc. mM)
form A solid
pka12.15±0.70(Predicted)
color White to light yellow
InChIKeyCEFJVGZHQAGLHS-UHFFFAOYSA-N
SMILESN(C1=CC(C2=CC3=C(N(CC)C2=O)C=C(NC)N=C3)=C(Br)C=C1F)C(NC1=CC=CC=C1)=O
Safety Information
MSDS Information
Ripretinib Usage And Synthesis
UsesRipretinib is used in the treatment of gastrointestinal stromal tumors (GISTs).
Brand nameQinlock
General DescriptionClass: receptor tyrosine kinase; Treatment: GIST; Other name: DCC-2618; Elimination half-life = 15 h; Protein binding = 98.8%
Biological ActivityRipretinib is a highly effective inhibitor of both wild-type KIT and PDGFRA, with IC50 values around 3 nM. It also targets a wide range of KIT and PDGFRA mutants in GIST. Additionally, it inhibits various tumor-driving kinases such as PDGFRβ, TIE2, VEGFR2, and BRAF.
SynthesisThe diethyl ester 297 was reacted with triethyl orthoformate and acetic anhydride by heating. Subsequent addition of aqueous ammonia afforded pyridine 298. Pyridine 298 was treated neat with phosphorus oxychloride at reflux to afford dichloride 299 in 90% yield. The 4-chloro group of pyridine 299 was selectively replaced by ethylamine in cooled acetonitrile to afford the product. Oxidation state adjustment using lithium aluminum hydride followed by MnO2 afforded 4-aminopyridine 300. Starting from acid 301, a three-step reaction process involving nitration, esterification, and reduction provided ester 302 directly. Ester 302 reacted with intermediate 300 in DMA (N,N-dimethylacetamide) with the aid of KF on alumina to form naphthyridinone ring system 303 via Knoevenagel cyclization. Methylamine groups were installed on naphthyridinone ring system 303. Reaction with phenylisocyanate to form urea completed the preparation of ripretinib.
Ripretinib synthesis
targetPrimary targets: PDGFRA, KIT
Ripretinib Preparation Products And Raw materials
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