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

HRID 1910943Notes

Reaction equation

HRID 1910943 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.[CH2:23](Cl)Cl.CB1OB(C)OB(C)O1.C1COCC1.[F-].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[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]([CH3:23])=[CH:3][CH:4]=2)[CH2:7]3)=[CH:16][CH:17]=1

Participants

9

Reactant 5

HCID 6344DichloromethaneHCID 8028TetrahydrofuranHCID 522689Potassium FluorideHCID 574072TrimethylboroxineHCID 67369880HCID 67369880, compound

Product 1

HCID 6737135210a-(4-methoxyphenyl)-8-methyl-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-oneYield 525.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a suspension of 8-bromo-10a-(4-methoxyphenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (60 mg, 0.17 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with CH2Cl2 (13 mg, 0.016 mmol) and trimethylboroxine solution in THF (3.5, M, 0.84 mmol, 0.24 mL) in 1,4-dioxane (1.5 mL) was added a solution of potassium fluoride (30 mg, 0.52 mmol) in water (0.5 mL). The reaction vessel was flushed with argon and then heated at 140° C. for 20 minutes in the microwave. The suspension was then diluted with CH2Cl2 and filtered. The organic layer was separated, dried (MgSO4), filtered and concentrated in vacuo to give a residue that was purified by flash chromatography (Biotage SP4, 12 g cartridge, CH2Cl2 3 CV, gradient 0-10% MeOH in CH2Cl2 15 CV) to give 10a-(4-methoxyphenyl)-8-methyl-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one as off-white solid (25 mg, yield 40%). ESI-MI m/z [M+H]+298.0.

Workup

  1. customThe reaction vessel was flushed with argon
  2. additionThe suspension was then diluted with CH2Cl2
  3. filtrationfiltered
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a residue that
  9. customwas purified by flash chromatography (Biotage SP4, 12 g cartridge, CH2Cl2 3 CV, gradient 0-10% MeOH in CH2Cl2 15 CV)

Sources & evidence

ORD record
ord-6f27ab9e03e34822943c8e984e4c54f8
Source dataset
uspto-grants-2013_12
Patent number
US08604034B2

Reaction notes

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