Potassium Iodide → 4-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-ethyl]-3'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

HRID 220536Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 220536
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+].[I-].[K+].Br[CH2:31][CH2:32][C:33]1[C:34]([CH3:39])=[N:35][NH:36][C:37]=1[CH3:38]>C(#N)C>[CH3:39][C:34]1[C:33]([CH2:32][CH2:31][N:19]2[CH2:18][CH2:17][N:16]([C:11]3[C:10]([C:7]4[CH:8]=[CH:9][C:4]([F:3])=[CH:5][CH:6]=4)=[N:15][CH:14]=[CH:13][N:12]=3)[CH2:21][CH2:20]2)=[C:37]([CH3:38])[NH:36][N:35]=1

Komponenten

6

Edukt 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 5728794-(2-Bromoethyl)-3,5-dimethyl-1H-pyrazoleHCID 673669583'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

Produkt 1

HCID 593218964-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-ethyl]-3'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinylAusbeute 0,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

Dissolve 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (0.200 g, 0.604 mmol) in acetonitrile (12 mL). Add potassium carbonate (0.334 g, 2.415 mmol), potassium iodide (0.005 g, 0.030 mmol), and 4-(2-bromo-ethyl)-3,5-dimethyl-1H-pyrazole (0.135 g, 0.664 mmol). Heat reaction at reflux for 14 hr. under nitrogen. Cool to room temperature and filter over celite. Concentrate filtrate in vacuo and purify residue by flash chromatography eluting with DCM:acetone 6:4 to afford the freebase as a mixture. Purify by reverse phase chromatography (43 g C-18, CH3CN: 1% aqueous TFA 5 to 95% over 20 min.) to afford a mixture. Purify by flash chromatography eluting with chloroform:methanol 0-10% to afford 4-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-ethyl]-3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.150 mg). Dissolve the free base (0.150 g, 0.394 mmol) in acetonitrile (1 mL) and add aqueous 1N HCl (0.433 mL, 0.433 mmol). Stir for 1 h at room temperature. Remove organics and lyophilize to afford the title compound (0.144 g, 77% yield). MS (m/z)=381 [M+H]+.

Aufarbeitung

  1. temperatureHeat
  2. customreaction
  3. temperatureat reflux for 14 hr
  4. filtrationfilter over celite
  5. customConcentrate filtrate in vacuo and purify residue by flash chromatography
  6. washeluting with DCM:acetone 6:4
  7. customto afford the freebase as a mixture
  8. customPurify by reverse phase chromatography (43 g C-18, CH3CN: 1% aqueous TFA 5 to 95% over 20 min.)
  9. customto afford a mixture
  10. customPurify by flash chromatography
  11. washeluting with chloroform

Quellen und Nachweise

ORD-Eintrag
ord-40c3ac2c9dd342c6a727c635d73d2332
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202873B2

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