2-Bromopyridine → HCID 67369193, compound

HRID 1753144Notes

Reaction equation

HRID 1753144 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]23[NH:29][CH2:28][CH2:27][N:9]2[C:10](=[O:26])[C:11]2[N:12]([CH:14]=[C:15](B4OC(C)(C)C(C)(C)O4)[CH:16]=2)[CH2:13]3)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=1>O1CCOCC1.O.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]23[NH:29][CH2:28][CH2:27][N:9]2[C:10](=[O:26])[C:11]2[N:12]([CH:14]=[C:15]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=4)[CH:16]=2)[CH2:13]3)=[CH:6][CH:7]=1

Participants

8

Reactant 3

HCID 79732-BromopyridineHCID 10796Cesium carbonateHCID 67367810HCID 67367810, compound

Product 1

HCID 67369193HCID 67369193, compoundYield 58.1%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension 10a-(4-methylphenyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (100 mg, 0.25 mmol) in 1,4-dioxane (3 mL) was degassed by flushing the reaction vessel with argon for 20 minutes. Cesium carbonate (165 mg, 0.51 mmol) in water (100 μL) was added followed by 2-bromopyridine (29 μL, 0.30 mmol). The mixture was flashed with argon prior adding bis(diphenylphosphino)ferrocene]dichloropalladium(II) (18 mg, 0.025 mmol). The mixture was heated at 100° C. for 2 hours. Water was added (5 mL) and the mixture extracted with CH2Cl2 (5 mL). The organic layer was dried (MgSO4), filtrated and concentrated in vacuo to give a residue that was purified by flash chromatography (Biotage SP4 gradient 0-5% MeOH in CH2Cl2) to give 10a-(4-methylphenyl)-7-(pyridin-2-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]-pyrazin-5-one (50 mg). The crude was used in the next step without purification. ESI-MI m/z [M+H]+ 345.1.

Workup

  1. customby flushing the reaction vessel with argon for 20 minutes
  2. extractionthe mixture extracted with CH2Cl2 (5 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltrated
  5. concentrationconcentrated in vacuo
  6. customto give a residue that
  7. customwas purified by flash chromatography (Biotage SP4 gradient 0-5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-c3779b602a7f4caebd35c5031060fcb8
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

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