Trimethylsilylacetylene → HCID 69201512, compound

HRID 900711Notes

Reaction equation

HRID 900711 reaction equation
[CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].[CH3:7][O:8][C:9](=[O:22])[CH2:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18](Br)[CH:19]=2)[CH:14]=[N:13][CH:12]=1>CN(C=O)C.C(N(CC)CC)C.C(OCC)(=O)C.[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>[CH3:7][O:8][C:9](=[O:22])[CH2:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1])[CH:19]=2)[CH:14]=[N:13][CH:12]=1

Participants

8

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 69199203HCID 69199203, compound

Product 1

HCID 69201512HCID 69201512, compound

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
45 °C

Procedure

Trimethylsilylacetylene (0.17 ml, 1.23 mmol) is added to a suspension of (6-bromo-isoquinolin-4-yl)-acetic acid methyl ester (0.325 g, 1.03 mmol) in DMF (1.75 ml) and triethylamine (10 ml), follwed by copper(I) iodide (40 mg, 0.20 mmol) and (Ph3P)2PdCl2 (73 mg, 0.10 mmol). The reaction is heated at 45° C. for 40 minutes, cooled to ambient temperature and diluted with ethyl acetate. After washing with water and brine, the organic phase is dried over, magnesium sulfate, evaporated and purified by flash column chromatography (1:1 ethyl acetate-hexane elution) to afford (6-trimethylsilanylethynyl-isoquinolin-4-yl)-acetic acid methyl ester, [MH]+ 298. This intermediate (0.221 g, 0.74 mmol) is dissolved in methanol (7.5 ml) and treated with potassium carbonate (75 mg, 0.54 mmol). The reaction is stirred for 30 minutes at ambient temperature, evaporated and purified by flash chromatography (5:1 dichloromethane-methanol elution) to afford (6-ethynyl-isoquinolin-4-yl)-acetic acid, [MH]+ 212.

Workup

  1. temperaturecooled to ambient temperature
  2. washAfter washing with water and brine
  3. dry with materialthe organic phase is dried over, magnesium sulfate
  4. customevaporated
  5. custompurified by flash column chromatography (1:1 ethyl acetate-hexane elution)

Sources & evidence

ORD record
ord-2c5478478fa84b8d8ec42fe930001f7a
Source dataset
uspto-grants-2008_04
Patent number
US07361661B2

Reaction notes

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