Sodium Iodide → N-{4-[4-(1,5-Dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-N-methyl-acetamide hydrochloride

HRID 220601

Reaktionsgleichung

Reaktionsgleichung von HRID 220601
[CH3:1][NH:2][C:3](=[O:5])[CH3:4].[H-].[Na+].Cl.Cl.[Cl:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([N:24]3[CH2:29][CH2:28][N:27]([CH2:30][C:31]4[CH:32]=[N:33][N:34]([CH3:37])[C:35]=4[CH3:36])[CH2:26][CH2:25]3)=[N:20][CH:21]=[CH:22][N:23]=2)=[CH:14][CH:13]=1.[I-].[Na+]>CN(C)C=O>[ClH:10].[CH3:37][N:34]1[C:35]([CH3:36])=[C:31]([CH2:30][N:27]2[CH2:28][CH2:29][N:24]([C:19]3[C:18]([C:15]4[CH:16]=[CH:17][C:12]([CH2:11][N:2]([CH3:1])[C:3](=[O:5])[CH3:4])=[CH:13][CH:14]=4)=[N:23][CH:22]=[CH:21][N:20]=3)[CH2:25][CH2:26]2)[CH:32]=[N:33]1

Komponenten

6

Edukt 4

HCID 5238Sodium IodideHCID 6582N-MethylacetamideHCID 24758Sodium hydrideHCID 685941603'-(4-chloromethyl-phenyl)-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

Produkt 1

HCID 68595410N-{4-[4-(1,5-Dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-N-methyl-acetamide hydrochlorideAusbeute 29 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Dissolve N-methyl acetamide (187 mg, 2.55 mmol) in dry N,N-dimethylformamide (5 mL) at room temperature under nitrogen. Add sodium hydride (60% dispersion in oil, 102 mg, 2.55 mmol), stir for 1 hr., then add 3′-(4-chloromethyl-phenyl)-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (300 mg, 0.64 mmol) and sodium iodide (96 mg, 0.64 mmol). Stir the reaction at 50° C. for 20 hr., the quench with water (10 mL). Extract with DCM (4×10 mL) and pass through an IST Phase Separator Frit®. Purify using SCX-2 chromatography, eluting with 3 M ammonia in methanol and further purify using silica gel chromatography (eluting with 5:95 methanol:DCM). Dissolve the clear oil in acetonitrile, and add 2 M aq. HCl and water then lyophilize to give the title compound as light yellow powder (87 mg, 29%). MS (ES): m/z=434 [M+H].

Aufarbeitung

  1. customthe reaction at 50° C. for 20 hr
  2. custom, the quench with water (10 mL)
  3. extractionExtract with DCM (4×10 mL)
  4. customPurify
  5. washeluting with 3 M ammonia in methanol
  6. customfurther purify
  7. washsilica gel chromatography (eluting with 5:95 methanol:DCM)
  8. dissolutionDissolve the clear oil in acetonitrile
  9. additionadd 2 M aq. HCl and water

Quellen und Nachweise

ORD-Eintrag
ord-fde6d1702c7c484ca917001a3413a701
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202873B2

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