C(OC([N:6]1[CH2:27][CH2:26][C:10]2[C:11]3[CH:12]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:13]([F:19])([F:18])[CH2:14][C:15]=3[CH:16]=[CH:17][C:9]=2[CH2:8][CH2:7]1)=O)C.Br>C(O)(=O)C>[F:19][C:13]1([F:18])[CH:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:11]2[C:10]3[CH2:26][CH2:27][NH:6][CH2:7][CH2:8][C:9]=3[CH:17]=[CH:16][C:15]=2[CH2:14]1Into a 250 ml flask, the product from step (e) (3.75 g, 10.10 mmol) dissolved in acetic acid (50 ml) and HBr (33% in acetic acid, 50 ml) was added. The reaction mixture was heated to 60° C. for 6 hours. The reaction mixture was cooled and the volatiles were evaporated in vacuo. The crude product was dissolved in water (100 ml) and washed with diethyl ether (3×). The aqueous layer was basified with 2M NaOH to pH 10 and then extracted with DCM (3×). The combined DCM extracts were washed with brine, dried over Na2SO4, and solvent evaporated in vacuo to give the title compound as tan oil (2.8 g) which solidified over time. 1H NMR (300 MHz, CDCl3) δ 7.32-7.26 (m, 3H); 7.10-7.07 (m, 2H); 7.02-6.99 (m, 2H); 4.62 (d, J=19.8 Hz, 1H); 3.44-3.35 (m, 2H); 2.99-2.83 (m, 4H); 2.73-2.64 (m, 2H); 2.58-2.45 (m, 2H); 2.33 (bs, 1H); MS: ESI (positive): 300 (M+1).
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