1H NMR 6 one methyl 1H imidazo pyridin two a single, 23, The general method A was followed employing six and 4 hydroxyphenylboronic acid to provide 23 as a dark yellow strong. 1H NMR six phenyl one methyl 1H imidazo pyridin 2 one hydrochloride, 25, The common method A was followed working with 6 and 4 phenylboronic acid to supply 25 as being a white strong, which was purified by flash chromatography employing reverse phase C13 column eluting having a linear gradient ranging from 0% to 100% Acetonitrile Water. 1H NMR benzamide, 26, The standard procedure A was followed using 6 and 4 carbamoylphenylboronic acid to supply 26 being a white reliable. 1H 3 benzoic acid, 27, A response mixture of six, phenyl boronic acid, Pd2 3, PCy3, and K3PO4 in dioxane was stirred under microwave heating for 1 h. The palladium catalyst was eliminated by filtration.
The filtrate was diluted with ethyl acetate and handled with one N HCl to acidify. The aqueous layer was eliminated, and after that the natural layer was washed with water and brine. The organic layer was dried more than magnesium sulfate, filtered, and concentrated in vacuo. Purification within the crude product by flash chromatography eluting having a linear selleck chemical Fingolimod gradient ranging from 25% to 100% EtOAc hexane provided six. 76 g of 27 as a yellow sound. 1H NMR 13. 07 benzoate, 28, To an answer of 27 and diisopropylethyl amine in dry CH2Cl2 was added pentafluorophenyl trifluoroacetate dropwise at 0 C. The mixture was stirred for 10 min, then was warmed for the ambient temperature and stirred for 1 h. The solvent was eliminated under lowered strain, then purification in the crude products by flash chromatography eluting with a linear gradient ranging from 6% to 50% EtOAc hexane yielded 0. 528 g of 28 as viscous yellow oil.
A solution of 28 in dry CH2Cl2 was prepared for the following amide formation Common Procedure BIBW2992 Afatinib B for Synthesis in the Substituted Benzamide Analogues in Scheme 3 To a solution of 28 and diisopropylethyl amine was additional the ideal main amine at 0 C. The reaction mixture was warmed for the ambient temperature and stirred for one h. The solvent was removed by diminished stress. The crude merchandise was diluted with ethyl acetate and washed with saturated aq. NaHCO3 and brine. The organic layer was dried more than magnesium sulfate, filtered, and concentrated in vacuo. Purification with the crude products by flash chromatography eluting by using a linear gradient ranging from 25% to 100% EtOAc hexane provided trityl protected benzamide analogues 29. To a solution of 29 in CH2Cl2 was added trifluoroacetic acid at room temperature. The reaction mixture was stirred for thirty min. After the solvent and trifluoroacetic acid were eliminated in vacuo, the desired product was purified by flash chromatography eluting wita linear gradient ranging from 0% to 20% MeOH EtOAc. h