Sodium Carbonate → Tert-butyl-[2-(5-trimethylsilanylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-amine

HRID 29111

Reaction equation

HRID 29111 reaction equation
[CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].Br[C:8]1[S:12][C:11]([C:13]2[N:14]=[C:15]3[CH:20]=[N:19][CH:18]=[CH:17][N:16]3[C:21]=2[NH:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:10][CH:9]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCN(CC)CC.CC(=O)OCC.[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>[C:23]([NH:22][C:21]1[N:16]2[CH:17]=[CH:18][N:19]=[CH:20][C:15]2=[N:14][C:13]=1[C:11]1[S:12][C:8]([C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1])=[CH:9][CH:10]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 66111TrimethylsilylacetyleneHCID 69317100[2-(5-Bromothiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-tert-butyl-amine

Product 1

HCID 69322358Tert-butyl-[2-(5-trimethylsilanylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-amineYield 65.1%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

21.4 ml (155 mmol) of trimethylsilylacetylene, 2.4 g (12.9 mmol) of copper(I) iodide and 4.5 g (6.5 mmol) of bis(triphenylphosphine)-palladium(II) chloride were added to a solution of 45.3 g (129 mmol) of [2-(5-bromo-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-tert-butyl-amine (synthesis described in Example 18, part a) in DMF (760 ml) and NEt3 (90 ml). The reaction solution was heated to 60° C. for 4 h and stirred at RT for 16 h. The mixture was then combined with a 1M aq. Na2CO3 solution and diluted with EA. The phases were separated and the aq. phase was extracted with EA. The combined organic phases were washed with water and dried over MgSO4. After filtration and removal of the solvents under a vacuum, the resultant group was redissolved with an EA/DCM (1:1) mixture and filtered through diatomaceous earth. The filtrate was evaporated under a vacuum. 30.8 g (84 mmol, 65%) of tert-butyl-[2-(5-trimethylsilanylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-amine were obtained from the group were by crystallisation from tert.-butyl-methyl ether.

Workup

  1. customsynthesis
  2. customThe phases were separated
  3. extractionthe aq. phase was extracted with EA
  4. washThe combined organic phases were washed with water
  5. dry with materialdried over MgSO4
  6. filtrationAfter filtration and removal of the solvents under a vacuum
  7. dissolutionthe resultant group was redissolved with an EA/DCM (1:1) mixture
  8. filtrationfiltered through diatomaceous earth
  9. customThe filtrate was evaporated under a vacuum

Sources & evidence

ORD record
ord-dfed8011b29e499095d725e08842eacf
Source dataset
uspto-grants-2008_09
Patent number
US07420056B2

Linked notes

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