O=S(Cl)Cl.[Br:5][C:6]1[CH:7]=[N:8][C:9]2[C:14]([CH:15]=1)=[C:13]([F:16])[C:12]([CH2:17][C:18](O)=[O:19])=[C:11]([F:21])[CH:10]=2.COC(=O)CC1C(F)=C2C(=CC=1F)N=CC(Br)=C2.[NH2:40][NH2:41]>CO>[Br:5][C:6]1[CH:7]=[N:8][C:9]2[C:14]([CH:15]=1)=[C:13]([F:16])[C:12]([CH2:17][C:18]([NH:40][NH2:41])=[O:19])=[C:11]([F:21])[CH:10]=2SOCl2 (394 mg, 3.31 mmol) was added dropwise to a stirred solution of (3-bromo-5,7-difluoro-quinolin-6-yl)-acetic acid (500 mg, 1.65 mmol) in 12 ml of methanol at 0° C. under N2. After stirring for 2 hours at room temperature the solvent was evaporated and the crude (3-bromo-5,7-difluoro-quinolin-6-yl)-acetic acid methyl ester was used directly in the next step. To a mixture of (3-bromo-5,7-difluoro-quinolin-6-yl)-acetic acid methyl ester (2.29 g, 7.22 mmol) in methanol (100 mL) was added anhydrous hydrazine (2.31 g, 72.2 mmol). The mixture was heated at 55° C. for 4 hours. Additional anhydrous hydrazine (1.16 g, 36.1) was added and the mixture was heated at 55° C. for 2 hours. The reaction mixture was cooled to room temperature to give a white solid. The white solid was filtered and washed with cold methanol to obtain 2.1 g of the title compound (92% yield). MS: m/z 318 [M+H+]. 1H NMR (500 MHz. DMSO-d6): δ 1.99 (2H, s), 4.25 (2H, bs), 7.72 (1H, d), 8.74 (1H, s), 9.03 (1H, s), 9.35 (1H, s).
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