Triethylamine → [2-(3-Hexyl-phenyl)-3-methyl-5-trimethylsilanylethynyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 545375Notes

Reaction equation

HRID 545375 reaction equation
[CH2:1]([C:7]1[CH:8]=[C:9]([C:13]2[N:17]([CH3:18])[C:16]([C:19]([N:21]3[CH2:26][CH2:25][CH:24]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:23][CH2:22]3)=[O:20])=[C:15](I)[N:14]=2)[CH:10]=[CH:11][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].CCN(CC)CC.[CH3:40][Si:41]([C:44]#[CH:45])([CH3:43])[CH3:42]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.[Cu]I.[Pd].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.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>[CH2:1]([C:7]1[CH:8]=[C:9]([C:13]2[N:17]([CH3:18])[C:16]([C:19]([N:21]3[CH2:26][CH2:25][CH:24]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:23][CH2:22]3)=[O:20])=[C:15]([C:45]#[C:44][Si:41]([CH3:43])([CH3:42])[CH3:40])[N:14]=2)[CH:10]=[CH:11][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 57541122[2-(3-Hexyl-phenyl)-5-iodo-3-methyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

Product 1

HCID 57541081[2-(3-Hexyl-phenyl)-3-methyl-5-trimethylsilanylethynyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

To a suspension of 0.55 g (1.00 mmol) of [2-(3-hexyl-phenyl)-5-iodo-3-methyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 2), 0.057 g (0.3 mmol) of copper(I) iodide, 0.117 g (0.1 mmol) of tetrakis-(triphenylphosphine)-palladium and 1.134 g (3.00 mmol) of tetrabutylammoniumiodide in 10 ml of DMF were added 2.027 ml=1.471 g (14.5 mmol) of Et3N. After stirring at RT for 30 min, 0.57 ml=0.394 g (4.0 mmol) of trimethylsilylacetylene were added and the reaction was heated up to 70° C. for 1 hour and subsequently cooled down to RT. The reaction mixture was then poured into crashed ice and extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1) to give 0.52 (100%) of the title compound as brown oil. MS: 519.4 (MH+).

Workup

  1. temperaturethe reaction was heated up to 70° C. for 1 hour
  2. temperaturesubsequently cooled down to RT
  3. additionThe reaction mixture was then poured
  4. extractionextracted twice with EtOAc
  5. washthe organic phases were washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1)

Sources & evidence

ORD record
ord-996f4db9ccce495593f9311cfc7daaf9
Source dataset
uspto-grants-2011_05
Patent number
US07935707B2

Reaction notes

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