反应详情

4-Methoxy-3,5-dimethylphenylboric acid (3.15 g; 17.5 mmol) followed by KF solution (2M in water, 15 ml) and finally Pd(PPh3)4 (607 mg; 0.525 mmol; 3 mol %) were added under a nitrogen atmosphere to a solution of 6-bromoimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (4.71 g; 17.5 mmol) in acetonitrile (30 ml) in a Milestone 100 ml high-pressure vessel. The reaction vessel was rinsed with nitrogen, closed and irradiated in a microwave at 160° C. for 5 min. (DC control: n-hexane-ethyl acetate 1:1). Four batches of the same size were run in parallel and combined prior to processing. The precipitated product was filtered out and washed with diethyl ether. The black crystalline product was taken up in chloroform and filtered over celite. The clear filtrate was concentrated to small volume and used for the next reaction without further purification. Yield: 22.7 g (quantitative). Stage 2. The 6-(4-methoxy-3,5-dimethylphenyl)-imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (22.7 g, 70 mmol) was dissolved in ethanol (300 ml) and NaOH solution (20% in water, 30 ml) was added. The reaction batch was refluxed for 24 hours. On completion of the reaction the solvent was removed in a rotary evaporator and the residue taken up in as small an amount of water as possible. The solution was carefully adjusted to pH 3-4 with HCl solution (10% in water). The precipitated product was filtered and washed with water. Yield: 21.2 (quantitative). Stage 3. Palladium on activated carbon (1 g) was added to a solution of 6-(4-methoxy-3,5-dimethylphenyl)-imidazo[1,2-a]pyridine-2-carboxylic acid (4.74 g; 16 mmol) in a blend of HCl (4% in water, 70 ml) and ethanol (140 ml). The mixture was poured into an autoclave (stainless steel), the autoclave was closed and rinsed a few times with nitrogen. The autoclave was filled with hydrogen (8 bar) and the reaction batch stirred for 12 h at room temperature. On completion of the reaction the catalyst was filtered out over celite and the solvent drawn off in a rotary evaporator at room temperature. The product was crystallized out of acetonitrile. Yield: 2.3 g (43%).

1. washThe reaction vessel was rinsed with nitrogen
2. customclosed
3. customirradiated in a microwave at 160° C. for 5 min. (DC control: n-hexane-ethyl acetate 1:1)
4. filtrationThe precipitated product was filtered out
5. washwashed with diethyl ether
6. filtrationfiltered over celite
7. concentrationThe clear filtrate was concentrated to small volume
8. customused for the next reaction without further purification
9. temperatureThe reaction batch was refluxed for 24 hours
10. customOn completion of the reaction the solvent
11. customwas removed in a rotary evaporator
12. filtrationThe precipitated product was filtered
13. washwashed with water
14. customthe autoclave was closed
15. washrinsed a few times with nitrogen
16. additionThe autoclave was filled with hydrogen (8 bar)
17. customOn completion of the reaction the catalyst
18. filtrationwas filtered out over celite
19. customthe solvent drawn off in a rotary evaporator at room temperature
20. customThe product was crystallized out of acetonitrile