Water → 4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-phenol

HRID 220566

Reaktionsgleichung

Reaktionsgleichung von HRID 220566
Cl[C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:16]=[N:17][N:18]([CH3:21])[C:19]=3[CH3:20])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[OH:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:21][N:18]1[C:19]([CH3:20])=[C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:3]3[C:2]([C:26]4[CH:27]=[CH:28][C:23]([OH:22])=[CH:24][CH:25]=4)=[N:7][CH:6]=[CH:5][N:4]=3)[CH2:9][CH2:10]2)[CH:16]=[N:17]1

Komponenten

7

Edukt 4

HCID 962Water2×HCID 11430Potassium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 594382163'-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

Produkt 1

HCID 1363515204-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-phenolAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

Stir together 3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (920 mg, 3.00 mmol), 4-(hydroxy)benzene boronic acid (497 mg, 3.6 mmol), potassium carbonate (996 mg, 7.2 mmol), tetrakis(triphenylphosphine)palladium(0) (0.018 g, 0.015 mmol) and water (6 mL) in N,N-dimethylacetamide (12 mL) at 120° C. for 5 hr. Cool to room temperature, add water (20 mL), extract with DCM (3×30 mL) and pass through an IST Phase Separator Frit®. Purify using SCX chromatography, eluting with 2.5 M ammonia in methanol and further purify using silica gel chromatography (eluting with 5:95 to 15:85 methanol:DCM). Concentrate and dry in a vacuum oven over night to give 4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenol as a light yellow powder (936 mg, 86%). MS (ES): m/z=365 [M+H].

Aufarbeitung

  1. extractionextract with DCM (3×30 mL)
  2. customPurify
  3. washeluting with 2.5 M ammonia in methanol
  4. customfurther purify
  5. washsilica gel chromatography (eluting with 5:95 to 15:85 methanol:DCM)
  6. concentrationConcentrate
  7. customdry in a vacuum oven over night

Quellen und Nachweise

ORD-Eintrag
ord-de60c1467c0b4a2396cce5d4696e64c3
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202873B2

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