Hydrochloric Acid → HCID 24716972, compound

Phenylboric acid (2.13 g; 17.5 mmol) followed by KF solution (2M in water, 15 ml) and finally Pd(PPh3)4 (607 mg; 0.5 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). Two 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 first over silica gel and then over celite. The clear filtrate was concentrated to dryness. Yield: 9.3 g (100%). Stage 2. The 6-phenylimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (9.32 g, 17.5 mmol) was dissolved in ethanol (80 ml) and NaOH solution (20% in water, 7 ml) was added. The reaction batch was refluxed for 8 hours. On completion of the reaction the solvent was removed in a rotary evaporator and the residue taken up in a small amount of water. The solution was carefully adjusted to pH 3-4 with HCl solution (10% in water). The precipitated product was filtered and washed with water and used in the next stage without further purification. Yield: 7.90 g (95%). Stage 3. Palladium on activated carbon (1.5 g) was added to a solution of 6-phenylimidazo[1,2-a]pyridine-2-carboxylic acid (6.3 g; 26.4 mmol) in a blend of HCl (4% in water, 100 ml) and ethanol (200 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 over the weekend at room temperature. 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: 4.1 g (56%).

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 first over silica gel
7. concentrationThe clear filtrate was concentrated to dryness
8. temperatureThe reaction batch was refluxed for 8 hours
9. customOn completion of the reaction the solvent
10. customwas removed in a rotary evaporator
11. filtrationThe precipitated product was filtered
12. washwashed with water
13. customused in the next stage without further purification
14. customthe autoclave was closed
15. washrinsed a few times with nitrogen
16. additionThe autoclave was filled with hydrogen (8 bar)
17. filtrationThe catalyst was filtered out over celite
18. customthe solvent drawn off in a rotary evaporator at room temperature
19. customThe product was crystallized out of acetonitrile

ORD record

ord-3ead517d29804daab75a75ad7ae0189e

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288424B2