Reaction Steps
A mixture of ethyl (2S)-2-(tert-butoxy)-2-{15,16-difluoro-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 (60 mg, 0.098 mmol) and NaOH (3.90 mg, 0.098 mmol) in EtOH (2 mL) was refluxed for 2 h. It was then cooled to rt and purified by preparative HPLC to isolate (2S)-2-(tert-butoxy)-2-{15,16-difluoro-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 (32.5 mg, 55.6%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.44-7.31 (m, 1H), 7.27 (dd, J=11.6, 8.6 Hz, 1H), 6.51 (s, 1H), 5.71 (s, 1H), 4.97-4.76 (m, 3H), 4.62 (d, J=12.5 Hz, 1H), 4.49 (t, J=11.2 Hz, 1H), 3.63-3.53 (m, 2H), 3.21-3.19 (m, 2H), 2.68-2.56 (m, 3H), 2.50 (br. s., 3H), 1.83 (d, J=12.8 Hz, 3H), 1.71-1.50 (m, 5H), 1.18 (s, 3H), 1.15 (s, 9H). LCMS (M+1)=587.3.
