反应详情

To a solution of isonicotinic acid 4 (100 mg, 0.496 mmol) and DIPEA (193 mg, 1.49 mmol) in DMF (2 mL), PyBOP (273 mg, 0.525 mmol) is added at 0° C. The mixture is stirred at 0° C. for 15 min before 3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenyl]-propionic acid tert-butyl ester (152 mg, 0.496 mmol) is added. The mixture is stirred at rt for 1 h before it is diluted with water and aq. NaHCO3 solution. The mixture is extracted twice with ether. The combined org. extracts are dried over MgSO4, filtered and concentrated to give the crude hydroxyamidine ester intermediate (420 mg); LC-MS: tR=0.90 min, [M+1]+=454.47. This material is dissolved in dioxane and then stirred at 80° C. for 5 h. The solvent is evaporated to give crude 3-{2-ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-propionic acid tert. butyl ester; LC-MS: tR=1.07 min, [M+1]+=436.25.

1. additionis added
2. extractionThe mixture is extracted twice with ether
3. dry with materialextracts are dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customto give the crude hydroxyamidine ester intermediate (420 mg)
7. stirringstirred at 80° C. for 5 h
8. customThe solvent is evaporated