Diisopropylamine → HCID 89444279, compound

HRID 593211Notes

Reaction equation

HRID 593211 reaction equation
Br[C:2]1[N: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(NC(C)C)(C)C.[C:24]([Si:26]([CH3:29])([CH3:28])[CH3:27])#[CH:25]>O1CCCC1.[Cu](I)I>[O:16]=[C:9]([NH:8][C:5]1[CH:4]=[N: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

6

Reactant 3

HCID 7912DiisopropylamineHCID 66111TrimethylsilylacetyleneHCID 89437205HCID 89437205, compound

Product 1

HCID 89444279HCID 89444279, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 4-[(5-bromopyrazin-2-yl)amino]-4-oxo-butanoate (A2, 1.0 g, 3.5 mmol), copper iodide (0.17 mmol, 0.033 g), diisopropylamine (4.2 mmol, 0.42 g, 0.59 mL) and palladium(II)bis(triphenylphosphine)dichloride (0.17 mmol, 0.12 g) in tetrahydrofuran (30 mL) was degassed with Ar. Then ethynyl(trimethyl)silane (7.60 mmol, 0.75 g, 1.1 mL) was added slowly and the mixture was stirred overnight. The mixture was filtered through a pad of celite which was washed with ethyl acetate and filtrate was concentrated under reduced pressure. The product was purified by flash chromatography (ethyl acetate/cyclohexane: 1/99→99/1) to give methyl 4-oxo-4-[[5-(2-trimethylsilylethynyl)pyrazin-2-yl]amino]butanoate (E, 0.85 g, 2.8 mmol, 80% Yield). 1H NMR (400 MHz, CDCl3) 9.46 (1H, s), 9.00 (1H, s), 8.33 (1H, s), 3.71 (3H, s), 2.88-2.75 (2H, m), 0.20 (9H, s).

Workup

  1. filtrationThe mixture was filtered through a pad of celite which
  2. washwas washed with ethyl acetate and filtrate
  3. concentrationwas concentrated under reduced pressure
  4. customThe product was purified by flash chromatography (ethyl acetate/cyclohexane: 1/99→99/1)

Sources & evidence

ORD record
ord-d760143028304bd49deec570863bd054
Source dataset
uspto-grants-2016_01
Patent number
US09241489B2

Reaction notes

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