Trimethylsilylacetylene → HCID 131733474, compound

HRID 2278976Notes

Reaction equation

HRID 2278976 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[C:23]([Si](C)(C)C)#[CH:24]>CN(C=O)C.CCOC(C)=O.[Cu]I>[C:23]([C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1)#[CH:24]

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 131733473HCID 131733473, compound

Product 1

HCID 131733474HCID 131733474, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A solution of tert-butyl (5-((2-chloropyridin-4-yl)oxy)pyridin-2-yl)carbamate (0.70 g, 2.18 mmol) in DMF (5 mL) was sparged with Ar, treated with ethynyltrimethylsilane (0.64 g, 6.55 mmol), TEA (1 mL), copper(I)iodide (0.042 g, 0.22 mmol) and trans dichlorobis(triphenylphosphine)palladium(0) (0.15 g, 0.22 mmol) and heated at 75° C., under Ar, overnight. The mixture was cooled to RT, diluted with EtOAc, the solids removed via filtration through diatomaceous earth and washed with EtOAc and water. The layers of the filtrate were separated, the aqueous layer extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The material was dissolved in MeOH (20 mL), treated with K2CO3 (0.7 g), stirred at RT for 2 h, then concentrated to dryness. The residue was treated with EtOAc, sonicated, the solids removed via filtration through diatomaceous earth, washed with EtOAc and the filtrate concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford tert-butyl (5-((2-ethynylpyridin-4-yl)oxy)pyridin-2-yl)carbamate (0.29 g, 43%). 1H NMR (400 MHz, DMSO-d6): δ 9.96 (s, 1 H), 8.41 (d, J=5.6 Hz, 1 H), 8.18 (d, J=2.8 Hz, 1 H), 7.88 (d, J=9.2 Hz, 1 H), 7.66 (m, 1 H), 7.07 (d, J=2.4 Hz, 1 H), 6.95 (m, 1 H), 4.34 (s, 1 H), 1.46 (s, 9 H); MS (ESI) m/z: 312.1 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. customthe solids removed via filtration through diatomaceous earth
  3. washwashed with EtOAc and water
  4. customThe layers of the filtrate were separated
  5. extractionthe aqueous layer extracted with EtOAc (2×)
  6. washthe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to dryness
  9. dissolutionThe material was dissolved in MeOH (20 mL)
  10. additiontreated with K2CO3 (0.7 g)
  11. concentrationconcentrated to dryness
  12. additionThe residue was treated with EtOAc
  13. customsonicated
  14. customthe solids removed via filtration through diatomaceous earth
  15. washwashed with EtOAc
  16. concentrationthe filtrate concentrated to dryness
  17. custompurified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-0e38bff988bf4881b9ebab19d2f83dd3
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

Loading…