Triethylamine → 10a-(4-methoxyphenyl)-8-[(trimethylsilyl)ethynyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one

HRID 1910944Notes

Reaction equation

HRID 1910944 reaction equation
Br[C:2]1[N:6]2[CH2:7][C:8]3([C:15]4[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=4)[NH:14][CH2:13][CH2:12][N:9]3[C:10](=[O:11])[C:5]2=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:30][Si:31]([C:34]#[CH:35])([CH3:33])[CH3:32]>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>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([C:8]23[NH:14][CH2:13][CH2:12][N:9]2[C:10](=[O:11])[C:5]2[N:6]([C:2]([C:35]#[C:34][Si:31]([CH3:33])([CH3:32])[CH3:30])=[CH:3][CH:4]=2)[CH2:7]3)=[CH:16][CH:17]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 67369880HCID 67369880, compound

Product 1

HCID 6736846710a-(4-methoxyphenyl)-8-[(trimethylsilyl)ethynyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-oneYield 67.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

8-bromo-10a-(4-methoxyphenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (120 mg, 0.33 mmol), Pd(PPh3)2Cl2 (23 mg, 0.033 mmol) and copper(I) iodide (15 mg, 0.079 mmol) were added to a 10 mL round bottom flask that was then evacuated and then filled back with argon twice. Dry DMF (5 mL) was added and the solution degassed with argon for 10 minutes. Triethylamine (0.24 mL, 1.7 mmol) and trimethylsilylacetylene (0.24 mL, 1.7 mmol) were added and the resulting brown solution was degassed with argon for a further minute. The reaction flask was sealed and heated at 80° C. until full consumption of the starting material (4 hours; monitored by LCMS). The solution was diluted with ethyl acetate (50 mL) and washed with brine (3×15 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give a material that was purified by flash chromatography (2× Biotage SP4, 12 g cartridge, CH2Cl2 3 CV, gradient 0-10% MeOH in CH2Cl2 15 CV, hold for 5 CV) and (Biotage SP4, 12 g cartridge, gradient 50-100% EtOAc in hexanes 10 CV, hold for 15 CV) to give 10a-(4-methoxyphenyl)-8-[(trimethylsilyl)ethynyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one as a yellow solid (84 mg, yield 62%). ESI-MI m/z [M+H]+ 380.0.

Workup

  1. customwas then evacuated
  2. additionfilled back with argon twice
  3. additionDry DMF (5 mL) was added
  4. customthe solution degassed with argon for 10 minutes
  5. customthe resulting brown solution was degassed with argon for a further minute
  6. customThe reaction flask was sealed
  7. additionThe solution was diluted with ethyl acetate (50 mL)
  8. washwashed with brine (3×15 mL)
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give a material that
  13. customwas purified by flash chromatography (2× Biotage SP4, 12 g cartridge, CH2Cl2 3 CV, gradient 0-10% MeOH in CH2Cl2 15 CV, hold for 5 CV) and (Biotage SP4, 12 g cartridge, gradient 50-100% EtOAc in hexanes 10 CV, hold for 15 CV)

Sources & evidence

ORD record
ord-64f9d8749674496cb22ccab357bb172b
Source dataset
uspto-grants-2013_12
Patent number
US08604034B2

Reaction notes

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