Methanol → HCID 71115123, compound

HRID 468874Notes

Reaction equation

HRID 468874 reaction equation
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[CH3:19])[CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([NH:20][C:21]([CH:23]1[CH2:25][CH2:24]1)=[O:22])[N:6]=[CH:7]2.F[B-](F)(F)F.F[B-](F)(F)F.C1(P(C2CCCCC2)CCCP(C2CCCCC2)C2CCCCC2)CCCCC1.[C:65](=[O:68])([O-])[O-:66].[K+].[K+].[CH3:71]O>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[CH:23]1([C:21]([NH:20][C:5]2[CH:4]=[C:3]3[C:8]([CH:9]=[C:10]([C:12]4[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=4[CH3:19])[N:11]=[C:2]3[C:65]([O:66][CH3:71])=[O:68])=[CH:7][N:6]=2)=[O:22])[CH2:25][CH2:24]1

Participants

8

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 57410130HCID 57410130, compoundHCID 71317487Phosphine, 1,1'-(1,3-propanediyl)bis[1,1-dicyclohexyl-, tetrafluoroborate(1-) (1:2)

Product 1

HCID 71115123HCID 71115123, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-(5-chloro-7-(5-fluoro-2-methylphenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide (50 mg, 0.14 mmol), palladium acetate (2 mg, 0.007 mmol), 1,3-bis(dicyclohexylphosphino)propane bis(tetrafluoroborate) (9 mg, 0.014 mmol), potassium carbonate (29 mg, 0.21 mmol), methanol (0.1 mL), and N,N-dimethylformamide (1 mL) was purged with nitrogen and evacuated (3×), flushed with carbon monoxide and evacuated (2×), and then left under a carbon monoxide balloon and heated at 100° C. for 2 hours. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane) to afford the title compound as a pale yellow solid (50 mg, 90%), which was used in the next step without further purification.

Workup

  1. customwas purged with nitrogen
  2. customevacuated (3×)
  3. customflushed with carbon monoxide
  4. customevacuated (2×)
  5. waitleft under a carbon monoxide balloon
  6. customThe cooled reaction mixture
  7. washwashed with water (100 mL)
  8. customThe organic layer was separated
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customto afford a residue that
  13. customwas purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-b1f15aa5959542b7aead9921de09c4eb
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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