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MRTX-849 Synthesis
MRTX-849 (Synonyms: 2-Piperazineacetonitrile, 4-[7-(8-chloro-1-naphthalenyl)-5,6,7,8-tetrahydro-2-[[(2S)-1-methyl-2-pyrrolidinyl]methoxy]pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoro-1-oxo-2-propen-1-yl)-, (2S)-)
MRTX-849 is a covalent inhibitor of K-RasG12C, a mutant form of K-Ras that accumulates in cancer cells.1 It binds to and stabilizes GDP-bound inactive K-RasG12C in an electrophoretic mobility shift assay when used at concentrations ranging from 2 to 15.6 nM. MRTX-849 (33-1,000 nM) reduces phosphorylation of the K-Ras targets ERK and S6 in MIA PaCa-2 cancer cells, which express K-RasG12C. In vivo, MRTX-849 (100 mg/kg) reduces tumor volume in 17 K-RasG12C-expressing lung, colon, pancreatic, cervical, and esophageal cancer mouse xenograft models but not wild-type K-Ras-expressing A549, HCT116, and H1299 mouse xenograft models.
MRTX-849
A covalent inhibitor of K-RasG12C
Item No. AZ90398
CAS No. 2326521-71-3
Purity: 98%
1mg
$40.00
10mg
$70.00
50mg
$268.00
100mg
$402.00
250mg
$694.00
1g
$1,736.00
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MRTX-849 Synthetic Route
AG74021
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AB46515
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AA91848
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AB44132
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A148416
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AB46644
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AH66868
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1: potassium iodide; triethylamine / toluene / 17 h / 90 °C
2: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 19 h / Heating
3: potassium hexamethylsilazane / toluene / 17 h / -35 - -33 °C
4: sodium methylate / methanol / 4 h / Reflux
5: sodium hydroxide / methanol / 2 h / 50 °C
6: sodium tungstate (VI) dihydrate; dihydrogen peroxide / water; acetonitrile / 17 h / 5 °C
7: sodium tert-pentoxide / 2-methyltetrahydrofuran / 15 h / 0 - 20 °C
8: caesium carbonate / 2-methyltetrahydrofuran / 2 h / -5 °C
9: potassium phosphate / N,N-dimethyl acetamide / 20 °C
10: 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / acetonitrile; ethyl acetate / 2 h / 10 - 20 °C
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Structure
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References
1.Org. Lett. 2023, 25, 944−949. 
2.Jones, J., Correll, D.J., Lechner, S.M., et al. Selective inhibition of NaV1.8 with VX-548 for acute pain. N. Engl. J. Med. 389(5), 393-405 (2023).