[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:26]C)=[C:6]2[C:10]=1[N:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17]CC3C=CC=CC=3)=[C:13]([F:25])[CH:12]=1)[N:8]=[CH:7]2.B(Br)(Br)Br>Br.C(OCC)(=O)C.C([O-])(O)=O.[Na+].O>[Cl:1][C:2]1[C:10]2[N:9]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([F:25])[CH:12]=3)[N:8]=[CH:7][C:6]=2[C:5]([OH:26])=[CH:4][CH:3]=1A mixture of 7-chloro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-(methyloxy)-1H-indazole (D29) (2.41 g, 6.30 mmol) in 48% hydrobromic acid (120 mL) was heated to reflux and reaction was followed by LC-MS. After 2 hrs, the mixture was concentrated to ˜30 mL on the rotary evaporator and then solid NaHCO3 was added to pH 6. The product was extracted into ethyl acetate and the extracts were dried (Na2SO4) and concentrated. This product was dissolved in dichloromethane (60 mL) and cooled to −78° C. under argon and boron tribromide (2.381 mL, 25.2 mmol) was added dropwise via syringe. After 10 mins at −78° C., the mixture was allowed to reach room temperature and stirring was continued for 24 hrs. The mixture was diluted with ethyl acetate and NaHCO3/water and the pH adjusted to 6 and the product was extracted into ethyl acetate. The extracts were dried (Na2SO4), concentrated and chromatographed (silica, 10% methanol in dichloromethane to crude product that was recolumned by 0-100% ethyl acetate in hexane) to give the title compound as an off-white powder (405 mg) (E14).
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