O=S(Cl)Cl.[Br:5][C:6]1[C:7]([O:22][CH2:23][CH2:24][C:25]([OH:27])=O)=[CH:8][CH:9]=[C:10]2[C:14]=1[N:13]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[N:12]=[CH:11]2.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[Br:5][C:6]1[C:7]2[O:22][CH2:23][CH2:24][C:25](=[O:27])[C:8]=2[CH:9]=[C:10]2[C:14]=1[N:13]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[N:12]=[CH:11]2SOCl2 (4.25 mL, 58.3 mmol) was added dropwise to a slurry of 3-((7-bromo-1-(4-fluorophenyl)-1H-indazol-6-yl)oxy)propanoic acid (98, R1=4-Fluorophenyl) (17.0 g, 44.8 mmol) and DCM (500 mL) under a nitrogen atmosphere at about 0° C. After about 10 min, the ice bath was removed. After about 1 h, SOCl2 (1.00 mL, 13.7 mmol) was added dropwise. After about 3 h, the solution was cooled to 0° C. and then aluminum chloride (18.0 g, 135 mmol) was added in three portions over about 15 min. The ice bath was allowed to thaw to rt over about 2 h. After about 1 h at rt, the mixture was poured into ice water (500 mL). After stirring for about 15 min, the layers were separated and the aqueous layer was extracted with DCM (100 mL). The combined organics were washed with water (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was slurried in EtOH (50 mL). The solid was collected by filtration rinsing with EtOH (2×10 mL) then dried under reduced pressure to afford 9-bromo-1-(4-fluorophenyl)-6,7-dihydropyrano[3,2-f]indazol-5(1H)-one (99, R1=4-Fluorophenyl) (13.3 g, 82% yield) as an ivory solid. LC/MS, method 3, Rt=2.26 min, MS m/z 361 and 363 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.50 (s, 1H), 8.42 (s, 1H), 7.61-7.54 (m, 2H), 7.42-7.33 (m, 2H), 4.66 (t, J=6.3 Hz, 2H), 2.89 (t, J=6.3 Hz, 2H).
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