Triethylamine → HCID 89812812, compound

HRID 717112Notes

Reaction equation

HRID 717112 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([C:13]1[CH:28]=[CH:27][C:16]([CH2:17][N:18]3[CH2:23][CH2:22][N:21]([C:24]([OH:26])=[O:25])[CH2:20][CH2:19]3)=[CH:15][CH:14]=1)[NH:6][C:7]2=[O:12].[C:29]([Si:31]([CH3:34])([CH3:33])[CH3:32])#[CH:30].[CH2:35](N(CC)CC)C.C1(P([C:55]2[CH:60]=[CH:59]C=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.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:60]([O:26][C:24]([N:21]1[CH2:22][CH2:23][N:18]([CH2:17][C:16]2[CH:15]=[CH:14][C:13]([C:5]3[NH:6][C:7](=[O:12])[C:8]4[C:3]([CH:4]=3)=[C:2]([C:30]#[C:29][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:11]=[CH:10][CH:9]=4)=[CH:28][CH:27]=2)[CH2:19][CH2:20]1)=[O:25])([CH3:59])([CH3:55])[CH3:35]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 117992667HCID 117992667, compound

Product 1

HCID 89812812HCID 89812812, compoundYield 973.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

4-[4-(5-Bromo-1-oxo-1,2-dihydro-isoquinolin-3-yl)benzyl]piperazine-1-carboxylic acid (140.0 mg, 0.281 mmol), ethynyltrimethylsilane (119 μL, 0.843 mmol), triethylamine (391 μL, 2.81 mmol), dichlorobis(triphenylphosphine)palladium(II) (19.6 mg, 0.028 mmol), and triphenylphosphine (3.67 mg, 0.014 mmol) in anhydrous DMF (3 mL) were added to a microwave vial and the reaction mixture purged with N2 for 5 min. Copper (I) iodide (5.33 mg, 0.028 mmol) was added and the mixture was degassed for a further minute. The reaction mixture was irradiated using a microwave reactor (300 W, 110° C., 1 h). The reaction mixture was then concentrated in vacuo, diluted with water (50 mL) and extracted with EtOAc (2×50 mL). The combined organic layer was washed with brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography, eluting with iso-hexane and increasing the polarity to 100% EtOAc/iso-hexane to afford 4-[4-(1-oxo-5-trimethylsilanylethynyl-1,2-dihydroisoquinolin-3-yl)benzyl]piperazine-1-carboxylic acid tert-butyl ester as a yellow solid (70.3 mg, 49%).

Workup

  1. customthe reaction mixture purged with N2 for 5 min
  2. customthe mixture was degassed for a further minute
  3. customThe reaction mixture was irradiated
  4. custom(300 W, 110° C., 1 h)
  5. concentrationThe reaction mixture was then concentrated in vacuo
  6. additiondiluted with water (50 mL)
  7. extractionextracted with EtOAc (2×50 mL)
  8. washThe combined organic layer was washed with brine (50 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude material was purified by silica gel column chromatography
  13. washeluting with iso-hexane
  14. temperatureincreasing the polarity to 100% EtOAc/iso-hexane

Sources & evidence

ORD record
ord-d4606dea2a6241c0baaf41ee9425ecb8
Source dataset
uspto-grants-2015_11
Patent number
US09193689B2

Reaction notes

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