Water → 3,7-Difluoro-8-(1-methylethenyl)-2-(methyloxy)-1,5-naphthyridine

HRID 15134Notes

Reaction equation

HRID 15134 reaction equation
Br[C:2]1[C:3]([F:15])=[CH:4][N:5]=[C:6]2[C:11]=1[N:10]=[C:9]([O:12][CH3:13])[C:8]([F:14])=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].O.N1C=C[CH:26]=[CH:25][CH:24]=1.CC(B1OB(C(C)=C)OB(C(C)=C)O1)=C>C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOCC>[F:14][C:8]1[C:9]([O:12][CH3:13])=[N:10][C:11]2[C:6]([CH:7]=1)=[N:5][CH:4]=[C:3]([F:15])[C:2]=2[C:25]([CH3:26])=[CH2:24]

Participants

8

Reactant 4

HCID 962Water2×HCID 11430Potassium CarbonateHCID 67526968Pyridine tris(1-methylethenyl)boroxinHCID 675272588-Bromo-3,7-difluoro-2-methoxy-1,5-naphthyridine

Product 1

HCID 675270293,7-Difluoro-8-(1-methylethenyl)-2-(methyloxy)-1,5-naphthyridine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 8-bromo-3,7-difluoro-2-(methyloxy)-1,5-naphthyridine (1.14 g, 4.15 mmol) and tetrakis(triphenylphosphine)palladium(0) (240 mg, 0.21 mmol) in degassed dimethoxyethane (40 ml) was stirred under argon for 30 minutes. Potassium carbonate (570 mg, 4.2 mmol), water (12 ml) and pyridine-tris(1-methylethenyl)boroxin (1:1) (470 mg, 1.66 mmol) were added the mixture was heated to reflux for 5 hours. The cooled mixture was treated with water (100 ml) and ether (200 ml). The phases were separated and the aqueous phase further extracted with ether (2×200 ml). The combined organic extracts were dried over magnesium sulphate and evaporated. The residue was chromatographed on silica eluting with a gradient of 0-50% ethyl acetate in hexane affording a white solid (820 mg, 84%).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 5 hours
  3. customThe phases were separated
  4. extractionthe aqueous phase further extracted with ether (2×200 ml)
  5. dry with materialThe combined organic extracts were dried over magnesium sulphate
  6. customevaporated
  7. customThe residue was chromatographed on silica eluting with a gradient of 0-50% ethyl acetate in hexane affording a white solid (820 mg, 84%)

Sources & evidence

ORD record
ord-92f46b2089c748f08d2779259d0f8b1f
Source dataset
uspto-grants-2010_06
Patent number
US07732460B2

Reaction notes

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