Water → N-{4-[4-(5-Methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-acetamide hydrochloride

HRID 220585Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 220585
[Cl:1][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]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:19]=3[CH3:20])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:33]([NH:36][CH2:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1)(=[O:35])[CH3:34].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>[ClH:1].[CH3:20][C:19]1[N:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:17]=[CH:16][C:15]=1[CH2:14][N:11]1[CH2:12][CH2:13][N:8]([C:3]2[C:2]([C:41]3[CH:42]=[CH:43][C:38]([CH2:37][NH:36][C:33](=[O:35])[CH3:34])=[CH:39][CH:40]=3)=[N:7][CH:6]=[CH:5][N:4]=2)[CH2:9][CH2:10]1

Komponenten

7

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 223094544-[(Acetylamino)methyl]benzeneboronic acidHCID 866416633'-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

Produkt 1

HCID 68594807N-{4-[4-(5-Methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-acetamide hydrochlorideAusbeute 96 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

Combine 3′-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.290 g, 0.786 mmol), potassium carbonate (0.261 g, 1.89 mmol), (4-acetamidomethylphenyl)boronic acid (0.182 g, 0.943 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.009 g, 0.008 mmol) in N,N-dimethylacetamide (1.6 mL). Add water (790 μL), and reflux reaction for 18 hr. Add DCM and wash with water. Extract water layer three times with DCM. Dry combined organics (magnesium sulfate) and purify (silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate:hexanes then 10:90 to 20:80 methanol:ethyl acetate), to give the free base of the title compound (365 mg, 96%). Dissolve the free base (0.363 g, 0.754 mmol) in acetonitrile (904 μL) and add aq. 1 N HCl solution (904 μL, 0.904 mmol). Shake for 15 min. at ambient temperature. Freeze dry to give the title compound (392 mg, 100%). MS (ES): m/z=482 [M+H]+.

Aufarbeitung

  1. customreaction for 18 hr
  2. washAdd DCM and wash with water
  3. customDry
  4. custompurify (silica gel chromatography
  5. washeluting with 50:50 to 100:0 ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-dd379698ce2e4cfd948a536552620e84
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202873B2

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