反应详情

温度

85 °C

Prepared using General Procedure 2. To a solution of 3-cyano-4-isopropoxybenzoic acid (0.033 g, 0.16 mmol) in DMF (1.0 mL) was added HOBt (0.036 g, 0.23 mmol) and EDC (0.045 g, 0.23 mmol) at room temperature. The reaction was stirred for 0.5 h until the complete formation of the HOBt-acid complex. 2-((Tert-butyldimethylsilyloxy)methyl)-N-hydroxyisonicotinimidamide INT-72 (0.050 g, 0.18 mmol) was added and the mixture was stirred at room temperature for 0.5 h until the formation of the intermediate 2-((tert-butyldimethylsilyloxy)methyl)-N-(3-cyano-4-isopropoxy benzoyloxy) isonicotinimidamide was observed. The reaction mixture was then heated at 85° C. for 4 h. To the cooled reaction mixture MeOH (1.0 mL) was added, and the solution was filtered. The resulting filtrate was purified by preparative HPLC to produce 5.6 mg (8%) of 5-(3-(2-(hydroxymethyl)pyridin-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 71 as the TFA salt. LCMS-ESI (m/z) calculated for C18H16N4O3: 336.3; found 337.1 [M+H]+, tR=7.45 min (Method 2). 1H NMR (400 MHz, CD3OD) δ 8.78 (d, J=5.5, 1H), 8.48 (dd, J=10.6, 8.3, 1.4, 3H), 8.23 (dd, J=5.5, 1.6, 1H), 7.48 (d, J=9.0, 1H), 4.93 (s, 2H), 4.89 (m, 1H), 1.48 (d, J=6.1, 6H).

1. customPrepared
2. additionwas added
3. filtrationthe solution was filtered
4. customThe resulting filtrate was purified by preparative HPLC