Triethylamine → [2-(5-Phenylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-(1,1,3,3-tetramethyl-butyl)-amine

HRID 29101Notes

Reaction equation

HRID 29101 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:8]=[C:9]3[CH:14]=[N:13][CH:12]=[CH:11][N:10]3[C:15]=2[NH:16][C:17]([CH3:24])([CH3:23])[CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:4][CH:3]=1.[C:25]1([C:31]#[CH:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.CC(=O)OCC.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.[Cu]I>[C:25]1([C:31]#[C:32][C:2]2[S:6][C:5]([C:7]3[N:8]=[C:9]4[CH:14]=[N:13][CH:12]=[CH:11][N:10]4[C:15]=3[NH:16][C:17]([CH3:24])([CH3:23])[CH2:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[CH:4][CH:3]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 10821PhenylacetyleneHCID 69316811[2-(5-Bromothiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-(1,1,3,3-tetramethyl-butyl)-amine

Product 1

HCID 69320956[2-(5-Phenylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-(1,1,3,3-tetramethyl-butyl)-amineYield 88%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

3.65 g (9.0 mmol) of [2-(5-bromothiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-(1,1,3,3-tetra-methyl-butyl)-amine were dissolved together with 1.18 ml (10.8 mmol) of phenylacetylene, 0.16 g (0.23 mmol) of bis(triphenylphosphine)-palladium(II) chloride and 0.08 g (0.45 mmol) of copper(I) iodide in DMF (30 ml). After addition of 2.50 ml (18.00 mmol) of triethylamine, the mixture was stirred at 50° C. for 16 h. The reaction solution was then diluted with EA and combined with a sat. aq. sodium carbonate solution. The phases were separated and the aqueous phase extracted with EA. The combined organic phases were washed 2× with a sat. aq. sodium carbonate solution and dried over magnesium sulfate. After filtration and removal of the solvents under a vacuum, column chromatography (EA/DIPE/DCM 3:3:4) was carried out with the group, after which 3.38 g (7.9 mmol, 88% of theoretical) of [2-(5-phenylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-(1,1,3,3-tetramethyl-butyl)-amine were obtained.

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase extracted with EA
  3. washThe combined organic phases were washed 2× with a sat. aq. sodium carbonate solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationAfter filtration and removal of the solvents under a vacuum, column chromatography (EA/DIPE/DCM 3:3:4)

Sources & evidence

ORD record
ord-0894d886c4874ca0992db3148468f96e
Source dataset
uspto-grants-2008_09
Patent number
US07420056B2

Reaction notes

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