5-BROMO-6-FLUORO-1H-BENZIMIDAZOLE

step 3: A mixture of 98 (600 mg, 2.93 mmol) in formic acid (5.0 mL) was heated to reflux overnight. The reaction mixture was concentrated in vacuo to afford a brown oil that was partitioned between EtOAc (300 mL) and a sat'd. aq. NaHC03 (100 mL). The organic layer was separated, dried (MgSO i), filtered and evaporated in vacuo to afford 550 mg (87percent) of 54oromo-6-fluoro-lH4oenzo[d]imidazole (100) as white solid (550 mg, 87percent): MS (ESI) m/z = 215 [M+l] +.step 4: A mixture of 100 (550 mg, 2.57 mmol), TsOH-H20 (50 mg, 0.26 mmol), and 3, 4-dihydro-2H- pyran (1.08 g, 12.85 mmol) in THF (10 mL) was heated at reflux overnight. After the solvent was removed in vacuo, the residue was partitioned between DCM (300 mL) and water (100 mL). The organic layer was separated, dried (MgSO i), filtered and concentrated in vacuo. The residue was purified by S1O2 chromatography eluting with a MeOH/DCM gradient (0.5 to 1% MeOH) to afford 817 mg (100%) of 5- bromo-6-fluoro-l -(tetrahydro-2H-pyran-2-yl)-lH-benzo[d]imidazole (102) as yellow oil: MS (ESI) m/z = 299 [M+l] +.To a solution of 5-bromo-6-fluoro-1-(triphenylmethyl)-1H-benzimidazole and 6-bromo-5-fluoro-1-(triphenylmethyl)-1H-benzimidazole (2.0 g, 4.4 mmol) in toluene (10 mL) under nitrogen atmosphere was added tetrakis(triphenylphosphine) palladium(0) (0.25 g, 0.2 mmol) followed by a solution of sodium bicarbonate (0.92 g, 11.0 mmol) in water (5 mL). A solution of 4-formylphenylboronic acid (0.72 g, 4.8 mmol) in ethanol (3 mL) was then added and the reaction was heated at reflux overnight. After removal of the solvent in vacuo, the residue was partitioned between ethyl acetate and water. The combined organics were dried over sodium sulfate, concentrated in vacuo, and purified via chromatography (20 to 50% ethyl acetate/hexanes) to provide the product as a mixture of trityl regioisomers, 4-[5-fluoro-1-(triphenylmethyl)-1H-benzimidazol-6-yl]benzaldehyde and 4-[6-fluoro-1-(triphenylmethyl)-1H-benzimidazol-5-yl]benzaldehyde.Isomer a: 1H NMR (400 MHz, CDCl3) delta 6.45-6.48 (m, 1H), 7.16-7.26 (m, 8H), 7.35-7.39 (m, 9H), 7.65-7.72 (m, 1H), 7.81 (d, J=7.4 Hz, 1H), 8.12-8.22 (m, 1H), 9.99 (s, 1H).Isomer b: 1H NMR (400 MHz, CDCl3) delta 6.27 (d, J=11.2 Hz, 1H), 7.17-7.21 (m, 6H), 7.34-7.37 (m, 9H), 7.70 (d, J=6.6 Hz, 2H), 7.85 (d, J=7.1 Hz, 1H), 7.92-7.96 (m, 3H), 10.04 (s, 1H).To a solution of step 3: A mixture of 98 (600 mg, 2.93 mmol) in formic acid (5.0 mL) was heated to reflux overnight. The reaction mixture was concentrated in vacuo to afford a brown oil that was partitioned between EtOAc (300 mL) and a sat'd. aq. NaHC03 (100 mL). The organic layer was separated, dried (MgSO i), filtered and evaporated in vacuo to afford 550 mg (87%) of 54oromo-6-fluoro-lH4oenzo[d]imidazole (100) as white solid (550 mg, 87%): MS (ESI) m/z = 215 [M+l] +.A solution of 4-bromo-5-fluoro-1, 2-benzenediamine (2.2 g, 10.7 mmol) in formic acid (5 mL) was heated at reflux for 2 h. The reaction was then cooled to room temperature and treated with 10% aq. NaOH until the mixture was basic. The dark mixture was extracted with ethyl acetate (3×), and the combined organics were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was triturated with dichloromethane, then dried under vacuum, providing the product, step 3: A mixture of 98 (600 mg, 2.93 mmol) in formic acid (5.0 mL) was heated to reflux overnight. The reaction mixture was concentrated in vacuo to afford a brown oil that was partitioned between EtOAc (300 mL) and a sat'd. aq. NaHC03 (100 mL). The organic layer was separated, dried (MgSO i), filtered and evaporated in vacuo to afford 550 mg (87%) of 54oromo-6-fluoro-lH4oenzo[d]imidazole (100) as white solid (550 mg, 87%): MS (ESI) m/z = 215 [M+l] +.A solution of 4-bromo-5-fluoro-1, 2-benzenediamine (2.2 g, 10.7 mmol) in formic acid (5 mL) was heated at reflux for 2 h. The reaction was then cooled to room temperature and treated with 10% aq. NaOH until the mixture was basic. The dark mixture was extracted with ethyl acetate (3×), and the combined organics were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was triturated with dichloromethane, then dried under vacuum, providing the product,

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