Tetrahydrofuran → 2-(Pyridin-2-yl)-3-(thiophen-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole

HRID 751281Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 751281
Br[C:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)=[N:5][N:4]2[CH2:13][CH2:14][CH2:15][C:3]=12.C1COCC1.[S:21]1[CH:25]=[CH:24][CH:23]=[C:22]1B(O)O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Pd].C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[N:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C:6]1[C:2]([C:22]2[S:21][CH:25]=[CH:24][CH:23]=2)=[C:3]2[CH2:15][CH2:14][CH2:13][N:4]2[N:5]=1

Komponenten

9

Edukt 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 27339602-Thiopheneboronic acidHCID 597100253-bromo-2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole

Produkt 1

HCID 99702112-(Pyridin-2-yl)-3-(thiophen-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoleAusbeute 5,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 2724231Bis(1,2-bis(diphenylphosphino)ethane)palladium(0)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 9832798Tris(dibenzylideneacetone) dipalladiumKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Add 3-bromo-2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (Preparation 4, 250 mg, 0.95 mmol) and anhydrous THF (2.5 mL) to a round bottom flask under nitrogen atmosphere. Purge the reaction flask with nitrogen for 10 min. Add tris(dibenzylideneacetone)dipalladium(0) (87 mg, 0.095 mmol) and bis(1,2-bis(diphenylphosphino)ethane) palladium(0) (86 mg, 0.095 mmol) to the reaction flask, purge with nitrogen for 2 min, and then stir at room temperature for 20 min. Add thiophene-2-boronic acid (Maybridge; 120 mg, 0.95 mmol) in DMF (1 mL) to the reaction and stir for 10 min. Add 2M aqueous potassium carbonate (1.11 mL, 2.3 mmol) and heat the reaction mixture to 65° C. Add additional tris(dibenzylideneacetone) dipalladium(0) (87 mg, 0.095 mmol) to the reaction after 1 h, 3 h, and 5 h. Heat the reaction for a total of 20 h, cool to room temperature, and filter through Celite® with chloroform/methanol (250 mL, 1:1 ratio). Concentrate in vacuo and purify by flash column chromatography to provide the title compound (13 mg, 5%) as a pale, yellow solid. MS ESI+ m/e 268 (M+1). 1H NMR (CDCl3) δ 8.80-8.72 (m, 1H), 7.80-7.56 (m, 2H), 7.31-7.20 (m, 2H), 7.12-7.03 (m, 1H), 7.01-6.95 (m, 1H), 4.31-4.19 (m, 2H), 3.11-3.05 (m, 2H), 2.79-2.60 (m, 2H). HPLC: 98.0%, Rt=15.25 min. TLC (SiO2): Rf0.4 (5:95 methanol/dichloromethane).

Aufarbeitung

  1. customPurge the reaction flask with nitrogen for 10 min
  2. stirringstir for 10 min
  3. temperatureheat the reaction mixture to 65° C
  4. customto the reaction after 1 h
  5. custom3 h, and 5 h
  6. temperatureHeat
  7. customthe reaction for a total of 20 h
  8. temperaturecool to room temperature
  9. filtrationfilter through Celite® with chloroform/methanol (250 mL, 1:1 ratio)
  10. concentrationConcentrate in vacuo
  11. custompurify by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-37647acf183449e48c841464d1d5d785
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07405299B2

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