Piperazine → HCID 57832787, compound

HRID 729499Notes

Reaction equation

HRID 729499 reaction equation
Br[C:2]1[N:7]2[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][CH:12]=3)[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.[NH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>CS(C)=O.C(OCC)(=O)C>[C:17]([C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:10]=[C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([N:21]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)[N:7]3[CH:8]=2)=[CH:12][CH:13]=1)([CH3:20])([CH3:19])[CH3:18]

Participants

5

Reactant 2

HCID 4837PiperazineHCID 578327855-Bromo-2-(4-tert-butyl-phenyl)-imidazo[1,2-a]pyridine

Product 1

HCID 57832787HCID 57832787, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

The mixture of isomeric bromides prepared in Example 17 (0.054 g, 0.165 mmol) was dissolved in DMSO (3.5 mL) and treated with piperazine (0.568 g, 6.60 mmol). The mixture was shaken at 160° C. overnight. The mixture was diluted with ethyl acetate (20 mL) and washed with 10% HCl (2×20 mL). The aqueous layers were separated, basified with saturated sodium carbonate and re-extracted with ethyl acetate (3×20 mL). The organic solution was dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 0.051 g of crude material. The crude material could be purified by semi-preparative RP-HPLC (Method C). The purified fractions were combined and concentrated under reduced pressure to remove acetonitrile. The aqueous residue was basified with saturated sodium carbonate and extracted with ethyl acetate (3×15 mL). The organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 13 mg (25%) of the title compound. Alternatively, the crude material could be used directly in the next step. HPLC (Method B): r.t.=6.2 min., purity 100% at 210-370 nm, 97.4% at 250 nm. HRMS: calcd for C21H26N4+H+, 335.22302; found (ESI, [M+H]+), 335.2228.

Workup

  1. washwashed with 10% HCl (2×20 mL)
  2. customThe aqueous layers were separated
  3. extractionre-extracted with ethyl acetate (3×20 mL)
  4. dry with materialThe organic solution was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto yield 0.051 g of crude material
  8. customThe crude material could be purified by semi-preparative RP-HPLC (Method C)
  9. concentrationconcentrated under reduced pressure
  10. customto remove acetonitrile
  11. extractionextracted with ethyl acetate (3×15 mL)
  12. dry with materialThe organic extracts were dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-49536887715846cf8a100fda94e5639f
Source dataset
uspto-grants-2009_09
Patent number
US07582636B2

Reaction notes

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