Dicyclohexylamine → 3-Ethynylimidazo[1,2-a]pyridine

Temperature

80 °C

To 3-bromoimidazo[1,2-a]pyridine (5 g, 0.0254 mol) in acetonitrile (50 mL) in a sealed tube was added bis(triphenylphosphine) palladium(II) dichloride (0.445 g, 0.634 mmol), Cul (0.17 g, 0.89 mmol), dicyclohexylamine (5.6 mL, 0.028 mol) and ethynyltrimethylsilane (7.2 mL, 0.051 mol). The solution was purged with argon for 15 minutes, sealed and heated at 80° C. for 3 h. At this point the HPLC did not show any starting bromide. The solvents were concentrated and to the residue was added water and dichloromethane (25 mL each). The organic layer was separated and the aqueous layer was repeatedly extracted with dichloromethane (3×20 mL). The combined extracts were dried (Na2SO4), and concentrated (Rf, 0.47 in 1/1 hexanes/ethyl acetate). The resulting residue was dissolved in THF (100 mL) and treated with tetrabutyl ammonium fluoride monohydrate (8.3 g, 0.032 mol) in water (5 mL) and the mixture was stirred at rt for 2 h. The solvents were concentrated and the resuting residue was partitioned between water (25 mL) and dichloromethane (150 mL). The aquesous layer was extracted with dichloromethane (2×30 mL). The combined extracts were dried (Na2SO4), and concentrated. The resulting residue was purified by combiflash on silica gel using hexanes/ethyl acetate. The desired product was eluted with 50/50 hexane/ethyl acetate and isolted as an off-white solid: MS (M+H)+ 200.

1. customThe solution was purged with argon for 15 minutes
2. customsealed
3. concentrationThe solvents were concentrated and to the residue
4. additionwas added water and dichloromethane (25 mL each)
5. customThe organic layer was separated
6. extractionthe aqueous layer was repeatedly extracted with dichloromethane (3×20 mL)
7. dry with materialThe combined extracts were dried (Na2SO4)
8. concentrationconcentrated (Rf, 0.47 in 1/1 hexanes/ethyl acetate)
9. dissolutionThe resulting residue was dissolved in THF (100 mL)
10. concentrationThe solvents were concentrated
11. customthe resuting residue was partitioned between water (25 mL) and dichloromethane (150 mL)
12. extractionThe aquesous layer was extracted with dichloromethane (2×30 mL)
13. dry with materialThe combined extracts were dried (Na2SO4)
14. concentrationconcentrated
15. customThe resulting residue was purified by combiflash on silica gel
16. washThe desired product was eluted with 50/50 hexane/ethyl acetate

ORD record

ord-1ba2598ffb8b43a59210b67eb2201e0a

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08114874B2