Sodium Hydroxide → 5-(3-(4-cyclopropyl-2-pyrimidinyl)-6-fluoro-1H-indol-5-yl)-N-(1-methylethyl)-1,3,4-oxadiazol-2-amine

Participants

Reaction Conditions

Reaction Steps

A 5 mL glass microwave tube was charged with 5-(3-(4-cyclopropylpyrimidin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (180 mg, 0.338 mmol) and treated with dioxane (2 mL) and 1 N NaOH (1 mL) and heated at 100° C. for 10 min in the microwave. The reaction mixture was treated with brine and extracted with EtOAc (2×20 mL), concentrated and purified by reverse phase using a Gilson automated platform (Silicycle Silichrome XT C18 column; 30×150 mm, 5 μm, 10-95% 0.1% TFA/CH3CN in 0.1% TFA/water by volume over 10 min), then dried in a Genevac Series II Evaporator affording the title compound (48.2 mg, 0.098 mmol, 29.0% yield) as a yellow amorphous solid. LC-MS (ESI, pos. ion) m/z: 379.2 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.93-12.03 (1H, m), 8.98 (1H, d, J=7.4 Hz), 8.59 (1H, d, J=5.1 Hz), 8.29 (1H, d, J=2.7 Hz), 7.85 (1H, d, J=7.4 Hz), 7.45 (1H, d, J=11.3 Hz), 7.21 (1H, d, J=5.3 Hz), 3.82 (1H, dq, J=13.2, 6.5 Hz), 2.13-2.22 (1H, m), 1.27 (6H, d, J=6.5 Hz), 1.20-1.25 (2H, m), 1.12-1.20 (2H, m). 19F NMR (377 MHz, DMSO-d6) δ ppm −74.90 (3F, s), −119.9 (1F, s).

Provenance & Evidence