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Sodium Carbonate → 7-Thiazol-2-yl-imidazo[1,2-a]pyridine

HRID 1446668
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1446668
Cl[C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[CH:9][N:10]=[C:4]2[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:60]1[S:61][CH:62]=[CH:63][N:64]=1>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[S:61]1[CH:62]=[CH:63][N:64]=[C:60]1[C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[CH:9][N:10]=[C:4]2[CH:3]=1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 6

HCID 10340Sodium CarbonateHCID 75806TricyclohexylphosphineHCID 764302-BromothiazoleHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 196959017-Chloroimidazo(1,2-a)pyridine

Produkt 1

HCID 68543434
7-Thiazol-2-yl-imidazo[1,2-a]pyridine
Ausbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel2×

Versuchsvorschrift

In a 500 mL round bottom flask, stir a suspension of 7-chloro-imidazo[1,2-a]pyridine (7.5 g, 49.2 mmol) in 250 mL 1,4-dioxane with bis(pinacolato)diboron (13.74 g, 54.1 mmol, 1.1 eq), potassium acetate (7.24 g, 73.8 mmol, 1.5 eq) and tricyclohexylphosphine (1.66 g. 5.9 mmol, 0.12 eq). Deoxygenate the resulting slurry with two cycles of evacuation and bubbling nitrogen through the slurry for 10 minutes each. Fit the flask with a reflux condenser and add tris(dibenzylidineacetone)dipalladium (0) (2.25 g, 2.45 mmol, 0.05 eq) and stir the mixture under nitrogen at 80° C. overnight. Filter the hot mixture over a ˜1 cm pad of celite, wash with 50 mL 1,4-dioxane, then concentrate the combined filtrate and wash to give a brown pasty solid. Suspend a portion of the solid (32.8 mmol) in 80 mL of dioxane, combine with 41.25 mL of 2 M aqueous sodium carbonate (82.5 mmol, 2.5 eq) and 2-bromothiazole (4.38 mL, 8.07 g, 49.2 mmol, 1.5 eq), then deoxygenate twice via evacuation and bubbling nitrogen through the suspension. Add tetrakis (triphenylphosphine) palladium (1.89 g, 1.64 mmol, 0.05 eq), fit the flask with a reflux condenser and stir the mixture under nitrogen at 100° C. overnight. Filter the dark brown-black hot mixture through a 1 cm pad of Celite®, wash with 50 mL dioxane, then apply the combined filtrate and wash equally to three 25 g SCX Mega Bond-Elut™ SCX cartridges (Varian) each pre-washed with 200 mL 1:1 CH2Cl2:MeOH. After loading with vacuum assist, wash each cartridge with 300 mL 1:1 CH2Cl2:MeOH, then elute with 160 mL 1:1 CH2Cl2:2 M NH3-MeOH. Concentrate the combined eluates in vacuo and purify through a 330 g silica gel cartridge using a 0 to 5% methanol gradient in dichloromethane. Concentrate the pooled clean fractions and dry to yield 3 g (45%) of 7-thiazol-2-yl-imidazo[1,2-a]pyridine as a tan solid. MS (ES) mm/z 202, (M+1).

Aufarbeitung

  1. customDeoxygenate the resulting slurry with two cycles of evacuation
  2. custombubbling nitrogen through the slurry for 10 minutes each
  3. stirringstir the mixture under nitrogen at 80° C. overnight
  4. filtrationFilter the hot mixture over a ˜1 cm pad of celite
  5. washwash with 50 mL 1,4-dioxane
  6. concentrationconcentrate the combined filtrate
  7. washwash
  8. customto give a brown pasty solid
  9. customdeoxygenate twice via evacuation
  10. custombubbling nitrogen through the suspension
  11. stirringstir the mixture under nitrogen at 100° C. overnight
  12. filtrationFilter the dark brown-black hot mixture through a 1 cm pad of Celite®
  13. washwash with 50 mL dioxane
  14. washapply the combined filtrate and wash equally to three 25 g SCX Mega Bond-Elut™ SCX cartridges (Varian)
  15. washeach pre-washed with 200 mL 1:1 CH2Cl2
  16. washwash each cartridge with 300 mL 1:1 CH2Cl2
  17. washMeOH, then elute with 160 mL 1:1 CH2Cl2
  18. concentrationConcentrate the combined eluates in vacuo
  19. custompurify through a 330 g silica gel cartridge
  20. concentrationConcentrate the pooled clean fractions
  21. customdry

Quellen und Nachweise

ORD-Eintrag
ord-b38e523d7b0c4cf8a2f40e9b018b4ffa
Quelldatensatz
uspto-grants-2010_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07666879B2

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