Potassium Phosphate, Tribasic → 1-(3-Imidazo[1,2-a]pyridin-3-yl-phenyl)-3-(2,2,2-trifluoro-ethyl)-urea

Temperature

90 °C

To a stirred solution of 3-Bromoimidazo[1,2-a]pyridine (commercially available, ex Bionet, 394 mg, 2 mmol) was added a solution of K3PO4 (1.27 g, 6 mmol) in H2O (2 mls). 1-[3-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-3-(2,2,2-trifluoro-ethyl)-urea (905 mg, 2.5 mmol) dissolved in dioxane (8 ml) was added to the reaction mixture and the reaction deoxygenated by evacuation and refill of the flask with N2 (×2). PdCl2dppf (150 mg, 0.2 mmol) was added and the reaction mixture was deoxygenated (×3). The reaction mixture was heated at 90° C. for 16 h, cooled to RT and partitioned between CH2Cl2 and H2O, then filtered. The layers were separated and the aqueous layer further extracted with CH2Cl2. The organic fractions were combined and passed through a phase separating cartridge, then the solvent removed in vacuo. The residue was purified using a SCX cartridge, washing with MeOH and eluting with 2M NH3/MeOH. The resulting solid was further purified by silica column chromatography (0-3% 2M NH3/MeOH in CH2Cl2) to afford a beige solid (335 mg). MS: [M+H]+=335.

1. additionwas added to the reaction mixture
2. customthe reaction deoxygenated by evacuation and refill of the flask with N2 (×2)
3. customthe reaction mixture was deoxygenated (×3)
4. temperaturecooled to RT
5. custompartitioned between CH2Cl2 and H2O
6. filtrationfiltered
7. customThe layers were separated
8. extractionthe aqueous layer further extracted with CH2Cl2
9. customseparating cartridge
10. customthe solvent removed in vacuo
11. customThe residue was purified
12. washwashing with MeOH
13. washeluting with 2M NH3/MeOH
14. customThe resulting solid was further purified by silica column chromatography (0-3% 2M NH3/MeOH in CH2Cl2)

ORD record

ord-d8d2ac7cafb14086bd66f3edf26a7572

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08131527B1