反应详情

To a suspension of 2-diethylamino-6-methylpyrimidine-4-carboxylic acid (1.31 g, 6.28 mmol) in DMF (20 mL) is added DIPEA (3.23 mL, 18.8 mmol) followed by TBTU (2.62 g, 8.17 mmol). The mixture is stirred at rt for 10 min before N-hydroxy-4-(2-hydroxy-ethyl)-benzamidine (1.24 g, 6.91 mmol) is added. After stirring for 1 h, the reaction mixture is diluted with EtOAc and the solution is washed with sat. aq. NaHCO3. The aq. phase is extracted with EtOAc and the combined org. extracts are dried over MgSO4, filtered and concentrated to give the crude hydroxyamidine ester intermediate (3.56 g). This material is dissolved in dioxane (50 mL) and the resulting solution is stirred at 85° C. for 16 h. The solvent is evaporated and the crude product is purified by CC (eluting with EtOAc/Heptane 1:4) to give 2-{4-[5-(2-diethylamino-6-methyl-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-ethanol as a yellow solid (1.30 g); LC-MS: tR=1.07 min; [M+H]+=354.07. 1H NMR (CDCl3): δ 1.25 (t, J=7.0 Hz, 6H), 1.45 (m, 1H), 2.47 (s, 3H), 2.98 (t, J=6.5 Hz, 2H), 3.75 (q, J=7.0 Hz, 4H), 3.95 (m, 2H), 7.23 (s, 1H), 7.41 (d, J=7.8 Hz, 2H), 8.15 (d, J=7.5 Hz, 2H).

1. additionis added
2. washthe solution is washed with sat. aq. NaHCO3
3. extractionThe aq. phase is extracted with EtOAc
4. dry with materialextracts are dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customto give the crude hydroxyamidine ester intermediate (3.56 g)
8. stirringthe resulting solution is stirred at 85° C. for 16 h
9. customThe solvent is evaporated
10. customthe crude product is purified by CC (eluting with EtOAc/Heptane 1:4)