Triethylamine → Methyl 4-oxo-4-[[5-(2-trimethylsilylethynyl)-2-pyridyl]amino]butanoate

HRID 525996Notes

Reaction equation

HRID 525996 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[N:6][CH:7]=1.C(N(CC)CC)C.[C:24]([Si:26]([CH3:29])([CH3:28])[CH3:27])#[CH:25]>O1CCCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[O:16]=[C:9]([NH:8][C:5]1[CH:4]=[CH:3][C:2]([C:25]#[C:24][Si:26]([CH3:29])([CH3:28])[CH3:27])=[CH:7][N:6]=1)[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 1506825Methyl 4-[(5-bromopyridin-2-yl)amino]-4-oxobutanoate

Product 1

HCID 89444199Methyl 4-oxo-4-[[5-(2-trimethylsilylethynyl)-2-pyridyl]amino]butanoateYield 10%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of methyl 4-[(5-bromo-2-pyridyl)amino]-4-oxo-butanoate (commercially available: 0.25 g, 0.871 mmol) in tetrahydrofuran was added bis(triphenylphosphine) palladium(II) dichloride (61.7536 mg, 0.087 mmol), copper(I) iodide (16.6 mg, 0.087 mmol), triethylamine (889 mg, 1.23 mL, 8.70 mmol) and ethynyltrimethylsilane (130 mg, 0.19 mL, 1.30 mmol). The reaction mixture was stirred at 65° C. overnight. The reaction was stopped and the solution was partitioned between ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate (2×). The combined organic layer was dried on magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography eluting with cyclohexane-ethyl acetate (3/1) to give methyl 4-oxo-4-[[5-(2-trimethylsilylethynyl)-2-pyridyl]amino]butanoate (26 mg, 10% yield). 1H NMR (400 MHz, CDCl3) 8.39 (s, 1H), 8.14 (m, 2H), 7.74 (d, 1H), 3.72 (s, 3H), 2.74 (m, 4H), 0.24 (s, 9H) ppm.

Workup

  1. customthe solution was partitioned between ethyl acetate and water
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (2×)
  4. customThe combined organic layer was dried on magnesium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by flash chromatography
  7. washeluting with cyclohexane-ethyl acetate (3/1)

Sources & evidence

ORD record
ord-423cd86b31384ec0b4e020671233f45a
Source dataset
uspto-grants-2016_05
Patent number
US09345244B2

Reaction notes

Loading…