Potassium Carbonate → Pyridine-3-sulfonic acid {2-[3'-(4-fluoro-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-amide hydrochloride

HRID 553514Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 553514
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:26])[S:17]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)(=[O:19])=[O:18])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.O.C(OCC)(=O)C.O>[ClH:1].[F:27][C:28]1[CH:33]=[CH:32][C:31]([C:2]2[C:3]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:26])[S:17]([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)(=[O:19])=[O:18])[CH2:10][CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:30][CH:29]=1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 86640207Pyridine-3-sulfonic acid [2-(3'-chloro-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-ethyl]-methyl-amide

Produkt 1

HCID 67368887Pyridine-3-sulfonic acid {2-[3'-(4-fluoro-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-amide hydrochlorideAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 21534740N,N-Dimethylacetamide--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

Dissolve pyridine-3-sulfonic acid [2-(3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl)-ethyl]-methyl-amide (0.200 g, 0.504 mmol) in DMA-H2O (4 mL; 3:1 v/v, previously degassed with nitrogen). Add 4-fluorophenyl boronic acid (0.084 g, 0.605 mmol), potassium carbonate (0.167 g, 1.209 mmol) and tetrakis(triphenyl-phosphine)palladium (0.029 g, 0.025 mmol). Stir the reaction mixture at 110° C. for 18 hr. Cool and dilute with ethyl acetate and water. Extract the aqueous layer with ethyl acetate and combine the organic layers. Dry the organics over sodium sulfate, filter, and concentrate. Purify by SCX chromatography, eluting with dichloromethane, dichloromethane:methanol, methanol, and 1N ammonia in methanol. Purify by silica gel chromatography eluting with hexanes:acetone 1:1 to afford the free base of the title compound (0.136 g, 59% yield).

Aufarbeitung

  1. custom3:1 v/v, previously degassed with nitrogen)
  2. temperatureCool
  3. extractionExtract the aqueous layer with ethyl acetate
  4. dry with materialDry the organics over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by SCX chromatography
  8. washeluting with dichloromethane, dichloromethane
  9. customPurify by silica gel chromatography
  10. washeluting with hexanes:acetone 1:1

Quellen und Nachweise

ORD-Eintrag
ord-4d72f4160c024dacb423e3255b478a5b
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08048884B2

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