5-BROMO-6-FLUORO-1H-INDAZOLE

The solution of l-(5-bromo-6-fluoro-lH-indazol-l-yl)ethanone (1.58 g, 6.15 mmol) in 3 M a.q. HC1 (20 mL) and MeOH (4 mL) was heated at 90 °C for 3 hours, then cooled to room temperature and basified with 1 M a.q. NaOH to pH = 10. A colorless solid precipitated out which was filtered and dried in vacuo to provide the desired product (1.22 g, 93 ).1H NMR (CDCIThe resulting indazole was suspended in 10percent HCl (70 mL) and methanol (ca. 20 mL) was added. The suspension was heated at reflux until clear (ca. Ih), at which time it was cooled and the pΗ increased by addition of sodium hydroxide (NaOH, 5 N) which caused an off-white solid to precipitate. The solution was filtered and the resulting solid was dried in vacuo to give the desired product (88d) in 84percent yield. LCMS (M+Η) 215.1 calc for CTo a stirred solution of 1-(5-bromo-6-fluoro-1H-indazol-1-yl)ethan-1-one (20 g, 78.43 mmol) in 3M HCl (400 mL) was added methanol (80 mL), reaction mixture was stirred at 90° C. for 3 h. j0626j A solution of 1-(5-bromo-6-fluoro-1H-indazol-1-yl)ethan-1-one (XXVII)(170 g, 629.9 mmol, 1.0 eq) in 3 N HC1 (6.6 mol, 10 eq) and MeOH (900 mL) was stirred at60°C for 12 h. TLC (PE:EtOAc = 5:1, Rf= 0.8) showed (XXVII) was consumed completely. Thereaction mixture was cooled to room temperature and basified with iN aq. NaOH to pH=10.The precipitated solid was filtered and dried in vacuo to afford 5-bromo-6-fluoro-1H-indazole(XXVIII) as a yellow solid (100 g, 465.1 mmol, 73.8percent yield). ESIMS found C7H4BrFN2 mlz 215.1(M+1).[0626] A solution of l-(5-bromo-6-fluoro-lH-indazol-l-yl)ethan-l-one (XXVII) (170 g, 629.9 mmol, 1.0 eq) in 3 N HCl (6.6 mol, 10 eq) and MeOH (900 mL) was stirred at 60°C for 12 h. TLC (PE:EtOAc = 5: 1, Rf = 0.8) showed (XXVII) was consumed completely. The reaction mixture was cooled to room temperature and basified with IN aq. NaOH to pH=10. The precipitated solid was filtered and dried in vacuo to afford 5-bromo-6-fluoro-lH-indazole (XXVIII) as a yellow solid (100 g, 465.1 mmol, 73.8percent yield). ESIMS found CA solution of l-(5-bromo-6-fluoro-lH-indazol-l-yl)ethan-l-one (XXVII) (170 g, 629.9 mmol, 1.0 eq) in 3 N HC1 (6.6 mol, 10 eq) and MeOH (900 inL) was stirred at 60°C for 12 h. TLC (PE:EtOAc = 5: 1, Rf = 0.8) showed (XXVII) was consumed completely. The reaction mixture was cooled to room temperature and basified with IN aq. NaOH to pH=10. The precipitated solid was filtered and dried in vacuo to afford 5-bromo-6-fluoro-lH-indazole (XXVIII) as a yellow solid (100 g, 465.1 mmol, 73.8percent yield). ESIMS found CA solution of l-(5-bromo-6-fluoro-lH-indazol-l-yl)ethan-l-one (XXVII) (170 g, 629.9 mmol, 1.0 eq) in 3 N HCl (6.6 mol, 10 eq) and MeOH (900 mL) was stirred at 60°C for 12 h. TLC (PE:EtOAc = 5: 1, Rf = 0.8) showed (XXVII) was consumed completely. The reaction mixture was cooled to room temperature and basified with IN aq. NaOH to pH=10. The precipitated solid was filtered and dried in vacuo to afford 5-bromo-6-fluoro-lH-indazole (XXVIII) as a yellow solid (100 g, 465.1 mmol, 73.8percent yield). ESIMS found CA solution of 1-(5-bromo-6-fluoro-1H-indazol-1-yl)ethan-1-one (XIX) (170 g, 629.9 mmol, 1.0 eq) in 3 N HCl (6.6 mol, 10 eq) and MeOH (900 mL) was stirred at 60° C. for 12 h. TLC (PE:EtOAc=5:1, Rf=0.8) showed (XIX) was consumed completely. The reaction mixture was cooled to room temperature and basified with 1N aq. NaOH to pH=10. The precipitated solid was filtered and dried in vacuo to afford 5-bromo-6-fluoro-1H-indazole (XX) as a yellow solid (100 g, 465.1 mmol, 73.8percent yield). ESIMS found CStep 4 (0809) A solution of 1-(5-bromo-6-fluoro-1H-indazol-1-yl)ethan-1-one (XIX) (170 g, 629.9 mmol, 1.0 eq) in 3 N HCl (6.6 mol, 10 eq) and MeOH (900 mL) was stirred at 60° C. for 12 h. TLC (PE:EtOAc=5:1, Rf=0.8) showed (XIX) was consumed completely. The reaction mixture was cooled to room temperature and basified with 1N aq. NaOH to pH=10. The precipitated solid was filtered and dried in vacuo to afford 5-bromo-6-fluoro-1H-indazole (XX) as a yellow solid (100 g, 465.1 mmol, 73.8percent yield). ESIMS found C

Molecular Weight:215.02
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:213.95419
Monoisotopic Mass:213.95419
Topological Polar Surface Area:28.7
Heavy Atom Count:11
Complexity:155
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes