Reaction Steps
A mixture of ethyl (2S)-2-(tert-butoxy)-2-{16-fluoro-4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.02,7.013,18]nonacosa-2,4,6(29),8,13(18),14,16-heptaen-3-yl}acetate (28 mg, 0.047 mmol) and NaOH (1.877 mg, 0.047 mmol) in EtOH (2 mL) was refluxed for 2 h. It was then cooler to rt and purified by preparative HPLC to obtain (2S)-2-(tert-butoxy)-2-{16-fluoro-4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.02,7.013,18]nonacosa-2,4,6(29),8,13(18),14,16-heptaen-3-yl}acetic acid (20 mg, 0.035 mmol, 75.0% yield) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.46-7.32 (m, 1H), 7.08-6.91 (m, 2H), 6.50 (s, 1H), 5.79 (s, 1H), 4.83 (q, J=12.1 Hz, 2H), 4.75 (d, J=12.5 Hz, 1H), 4.61 (d, J=12.5 Hz, 1H), 4.49 (t, J=11.7 Hz, 1H), 3.69-3.32 (m, 3H), 3.07 (br. s., 1H), 2.69 (br. s., 2H), 2.56 (d, J=9.5 Hz, 1H), 2.51 (br. s., 3H), 1.87-1.50 (m, 8H), 1.18 (s, 3H), 1.16 (s, 9H). LCMS (M+1)=569.2.
