Reaction Steps
A mixture of ethyl (2S)-2-(tert-butoxy)-2-{16-fluoro-4,25-dimethyl-11,24-dioxa-1,5,7,8-tetraazapentacyclo[23.2.2.16,9.02,7.013,18]triaconta-2,4,6(30),8,13(18),14,16-heptaen-3-yl}acetate (36 mg, 0.059 mmol) and NaOH (0.295 mL, 0.295 mmol) in EtOH (2 mL) was refluxed for 2 h. It was then filtered and purified by preparative HPLC to obtain (2S)-2-(tert-butoxy)-2-{16-fluoro-4,25-dimethyl-11,24-dioxa-1,5,7,8-tetraazapentacyclo[23.2.2.16,9.02,7.013,18]triaconta-2,4,6(30),8,13(18),14,16-heptaen-3-yl}acetic acid (23.3 mg, 0.040 mmol, 67.8% yield) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.37-7.29 (m, 1H), 7.04 (d, J=9.9 Hz, 1H), 6.95 (t, J=8.3 Hz, 1H), 6.49 (s, 1H), 5.59 (s, 1H), 4.72-4.66 (m, 1H), 4.65-4.57 (m, 3H), 4.45 (t, J=11.7 Hz, 1H), 3.58-3.30 (m, 4H), 2.84-2.75 (m, 1H), 2.66 (d, J=12.8 Hz, 2H), 2.50 (br. s., 3H), 1.93-1.88 (m, 1H), 1.83 (d, J=13.9 Hz, 1H), 1.70-1.49 (m, 8H), 1.19 (s, 3H), 1.14 (s, 9H). LCMS (M+1)=583.7.
