[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][C:17]([O:20]C)=[C:16]([F:22])[C:15]=3[F:23])[N:12]=[N:11][N:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.B(Br)(Br)Br>C(Cl)Cl>[NH2:8][C:5]1[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([F:22])[C:15]=3[F:23])[N:12]=[N:11][N:10]=2)=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1As shown in step 4-i of Scheme 4,5-bromo-3-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)pyridin-2-amine (Compound 1005, 20.0 g, 7.663 mmol) in 150 mL of DCM was cooled 0° C. Boron tribromide (20.0 mL of a 1M solution in DCM, 20 mmol) was added dropwise. After the addition was complete, the reaction mixture was warmed to room temperature and stirred for 48 hours. The reaction was carefully quenched with crushed ice and extracted with EtOAc (3×200 mL). The combined organics were washed with water, washed with brine, and dried over sodium sulfate. After filtration, the volatiles were removed under reduced pressure to yield a brown solid, which was triturated with pentane to yield 4-(5-(2-amino-5-bromopyridin-3-yl)-1H-tetrazol-1-yl)-2,3-difluorophenol (Compound 1016) as a pale brown solid.
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