Propargyl alcohol → HCID 66736239, compound

HRID 1640503Notes

Reaction equation

HRID 1640503 reaction equation
Br[C:2]1[CH:3]=[CH:4][N:5]=[C:6]2[C:11]=1[N:10]=[C:9]([O:12][CH3:13])[CH:8]=[CH:7]2.[CH2:14]([OH:17])[C:15]#[CH:16]>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][CH:3]=[C:2]2[C:16]#[C:15][CH2:14][OH:17]

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 534216178-Bromo-2-methoxy-1,5-naphthyridine

Product 1

HCID 66736239HCID 66736239, compoundYield 54.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 8-bromo-2-methoxy-[1,5]naphthyridine (4.0 g, 16.7 mmol, prepared as in WO 2006/032466) and propargylalcohol (1.9 g, 33.5 mmol) in DMF (50 mL) and TEA (10.16 g, 100 mmol) was degassed by bubbling N2 through for 10 min. CuI (0.318 g, 1.6 mmol) and Pd(PPh3)2Cl2 (0.588 g, 0.84 mmol) were added and the brown solution was stirred at rt overnight. The mixture was partitioned between water and EtOAc and the org. layer was washed several times with water and a sat. NH4Cl solution, dried over MgSO4 and concentrated. Chromatography on SiO2 (Hex/EA 1:1, EA) followed by crystallization from ether gave the coupling product as a beige solid (1.95 g, 54% yield).

Workup

  1. customby bubbling N2 through for 10 min
  2. customThe mixture was partitioned between water and EtOAc
  3. washlayer was washed several times with water
  4. dry with materiala sat. NH4Cl solution, dried over MgSO4
  5. concentrationconcentrated
  6. customChromatography on SiO2 (Hex/EA 1:1, EA) followed by crystallization from ether

Sources & evidence

ORD record
ord-da2ebaf2f4ef4bb8a2b10a33655bf44e
Source dataset
uspto-grants-2012_02
Patent number
US08114867B2

Reaction notes

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