Phenylacetylene → HCID 24970980, compound

HRID 1468566Notes

Reaction equation

HRID 1468566 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]([C:13]2[CH:18]=[CH:17][C:16](I)=[CH:15][CH:14]=2)=[CH:11][N:10]=[C:9]1[NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[C:37]1([C:43]#[CH:44])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1COCC1.[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:1]([O:5][C:6]([N:8]1[C:12]([C:13]2[CH:18]=[CH:17][C:16]([C:44]#[C:43][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:15][CH:14]=2)=[CH:11][N:10]=[C:9]1[NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10821PhenylacetyleneHCID 81531DiisopropylethylamineHCID 57931422HCID 57931422, compound

Product 1

HCID 24970980HCID 24970980, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

2-tert-butoxycarbonylamino-5-(4-iodophenyl)imidazole-1-carboxylic acid tert-butyl ester (0.100 g, 0.206 mmol) was dissolved in anhydrous THF (8 mL) and to this solution was added DIPEA (0.359 mL, 2.06 mmol), CuI (0.004 g, 0.021 mmol), and PdCl2(PPh3)2 (0.014 g, 0.021 mmol). The solution was then degassed at ambient temperature for 10 minutes. During this time a solution of the phenyl acetylene (0.105 g, 1.03 mmol) in anhydrous THF (3 mL) was also degassed. The solution of alkyne was added drop-wise to the solution of aryl iodide and the reaction was stirred at room temperature for 12 h. The reaction was filtered through a Celite® pad and the filter cake rinsed with EtOAc (10 mL). The filtrate was washed with sat. NH4Cl (2×10 mL), brine (2×10 mL), and dried (Na2SO4). Filtration and evaporation afforded the crude product which was purified via flash column chromatography (10-50% EtOAc/Hexanes) to obtain 0.085 g (90%) of the target 2-tert-butoxycarbonylamino-5-(4-phenylethynylphenyl) imidazole-1-carboxylic acid tert-butyl ester as a yellow solid: mp=131-132° C.; 1H NMR (400 MHz, DMSO-d6) δ 9.60 (s, 1H), 8.00 (s, 1H), 7.86 (d, 2H, J=7.6 Hz), 7.42-7.57 (m, 7H), 1.58 (s, 9H), 1.44 (s, 9H); 13C NMR (100 MHz, DMSO-d6) δ 152.9, 146.8, 139.9, 136.3, 133.0, 131.7, 131.4, 128.8, 124.9, 122.4, 126.8, 120.9, 113.7, 89.9, 89.5, 85.4, 80.1, 27.9, 27.3; HRMS (ESI) calcd for C27H19N3O4Na (MNa+) 482.2050. found 482.2051.

Workup

  1. customThe solution was then degassed at ambient temperature for 10 minutes
  2. filtrationThe reaction was filtered through a Celite® pad
  3. washthe filter cake rinsed with EtOAc (10 mL)
  4. washThe filtrate was washed with sat. NH4Cl (2×10 mL), brine (2×10 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationFiltration and evaporation
  7. customafforded the crude product which
  8. customwas purified via flash column chromatography (10-50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-d52ec1095461444583093a2c3ad31e6f
Source dataset
uspto-grants-2015_04
Patent number
US09005643B2

Reaction notes

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