Potassium Carbonate → 3'-(4-fluoro-phenyl)-4-[3-(1-methyl-1H-pyrazol-4-yl)-propyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

HRID 220537Notes

Reaction equation

HRID 220537 reaction equation
Cl.Cl.[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[N:12][CH:13]=[CH:14][N:15]=2)=[CH:6][CH:5]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:29][CH2:30][CH2:31][C:32]1[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=1>C(#N)C.[I-].[K+]>[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]([N:16]3[CH2:17][CH2:18][N:19]([CH2:29][CH2:30][CH2:31][C:32]4[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=4)[CH2:20][CH2:21]3)=[N:12][CH:13]=[CH:14][N:15]=2)=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 457914634-(3-bromopropyl)-1-methyl-1H-pyrazoleHCID 673669583'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

Product 1

HCID 593220433'-(4-fluoro-phenyl)-4-[3-(1-methyl-1H-pyrazol-4-yl)-propyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinylYield 84.4%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 6342AcetonitrileSolvent

Procedure

Dissolve 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (0.200 g, 0.604 mmol) in acetonitrile (10 mL). Add potassium carbonate (0.334 g, 2.415 mmol), potassium iodide (0.005 g, 0.030 mmol), and 4-(3-bromo-propyl)-1-methyl-1H-pyrazole (0.184 g, 0.906 mmol). Heat reaction at reflux for 14 hr. under nitrogen. Cool to room temperature and partition between water and ethyl acetate. Separate and extract aqueous with ethyl acetate. Combine organic portions, dry over sodium sulfate, filter, and concentrate in vacuo. Purify residue by flash chromatography eluting with chloroform:methanol 19:1 to afford 3′-(4-fluoro-phenyl)-4-[3-(1-methyl-1H-pyrazol-4-yl)-propyl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.194 g). Dissolve in acetonitrile (1 mL) and add aqueous 1N HCl (0.561 mL, 0.561 mmol). Stir for 1 h at room temperature. Remove organics and lyophilize to afford the title compound (0.189 g, 75% yield). MS (m/z)=381[M+H]+.

Workup

  1. temperatureHeat
  2. customreaction
  3. temperatureat reflux for 14 hr
  4. custompartition between water and ethyl acetate
  5. customSeparate
  6. extractionextract aqueous with ethyl acetate
  7. dry with materialCombine organic portions, dry over sodium sulfate
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. washPurify residue by flash chromatography eluting with chloroform:methanol 19:1

Sources & evidence

ORD record
ord-c9c6b0a167aa4b46873f376d70108487
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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