反应详情

To a round bottomed flask, add 1-(4-bromo-phenyl)-3-(5-tert-butyl-2H-pyrazol-3-yl)-urea (0.41 g, 1.2 mmol), tricyclohexylphosphine (24 mg, 0.07 equiv.), potassium acetate (0.36 g, 3 equiv.), bis(pinacolato)diboron (0.34 g, 1.1 equiv.) and DMSO (5 mL). Deoxygenate this mixture thoroughly with N2 then add tris(dibenzylideneacetone)-di-palladium (0) (33 mg, 0.03 equiv.) and heat to 100° C. overnight. Dilute the reaction with EtOAc and wash with water then saturated aqueous saturated sodium chloride. Pass the organic layer thru a Celite® plug then dry over magnesium sulfate, filter and concentrate to a residue (0.72 g). MS (ES), m/z 385.4 (M+1) is present. Add to this residue 3-iodo-7-(4-methanesulfonyl-phenyl)-imidazo[1,2-a]pyridine (0.25 g, 0.62 mmol), potassium carbonate (0.26 g, 1.86 mmol), dioxane (10 mL), and water (5 mL). Deoxygenate this mixture thoroughly with N2 then add dichloro-bis(triphenylphosphine) palladium (II) (13 mg, 0.03 equiv.) and reflux the reaction overnight under N2. Concentrate the reaction to dryness and slurry in acetone and filter to remove insolubles. Concentrate the filtrate then purify by silica column (1:1 Hex:EtOAc to 1:2 Hex:EtOAc to EtOAc to 5% MeOH:DCM) to give crude product. Triturate from DCM to give a pale yellow solid (0.059 g, 18%). MS (ES), m/z 529 (M+1).

1. customDeoxygenate this mixture thoroughly with N2
2. additionDilute
3. washwash with water
4. dry with materialthen dry over magnesium sulfate
5. filtrationfilter
6. concentrationconcentrate to a residue (0.72 g)
7. customDeoxygenate this mixture thoroughly with N2
8. customthe reaction overnight under N2
9. concentrationConcentrate
10. customthe reaction to dryness and slurry in acetone
11. filtrationfilter
12. customto remove insolubles
13. concentrationConcentrate the filtrate
14. customthen purify by silica column (1:1 Hex:EtOAc to 1:2 Hex:EtOAc to EtOAc to 5% MeOH:DCM)
15. customto give crude product
16. customTriturate from DCM