3-bromobenzene-1,2-diamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromobenzene-1,2-diamine (1.00 g, 5.35 mmol, CombiBlocks, Inc., San Diego, Calif.) and methyl 3,3,3-trifluoro-2-oxopropanoate (0.655 mL, 6.42 mmol; Alfa Aesar, Ward Hill, Mass.) in EtOH (15 mL) was stirred at reflux under argon for 17 h. The mixture was concentrated in vacuo. Purification by silica gel (0-70% EtOAc/Hexanes) provided 8-bromo-3-(trifluoromethyl)quinoxalin-2(1H)-one (224b, 29% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.43 (1H, br. s.), 8.04 (1H, d, J=7.8 Hz), 7.95 (1H, d, J=8.2 Hz), 7.38 (1H, t, J=7.9 Hz). 19F NMR (377 MHz, DMSO-d6) δ ppm −68.44 (3F, br. s.). MS (ESI, pos. ion) m/z: 293.0 (M+1). at reflux under argon for 17 h The mixture was concentrated in vacuo Purification by silica gel (0-70% EtOAc/Hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromobenzene-1,2-diamine (1.00 g, 5.35 mmol, CombiBlocks, Inc., San Diego, Calif.) and methyl 3,3,3-trifluoro-2-oxopropanoate (0.655 mL, 6.42 mmol; Alfa Aesar, Ward Hill, Mass.) in EtOH (15 mL) was stirred at reflux under argon for 17 h. The mixture was concentrated in vacuo. Purification by silica gel (0-70% EtOAc/Hexanes) provided 8-bromo-3-(trifluoromethyl)quinoxalin-2(1H)-one (224b, 29% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.43 (1H, br. s.), 8.04 (1H, d, J=7.8 Hz), 7.95 (1H, d, J=8.2 Hz), 7.38 (1H, t, J=7.9 Hz). 19F NMR (377 MHz, DMSO-d6) δ ppm −68.44 (3F, br. s.). MS (ESI, pos. ion) m/z: 293.0 (M+1). at reflux under argon for 17 h The mixture was concentrated in vacuo Purification by silica gel (0-70% EtOAc/Hexanes)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromobenzene-1,2-diamine (2 g, 10.7 mmol) in HCOOH was stirred at 100° C. for 1 h. The mixture was cooled and concentrated in vacuo and diluted with ethyl acetate and aq. NaHCO3. The mixture was extracted further with ethyl acetate and the combined organic layers dried and concentrated to give the crude product which was purified by column chromatography to obtain the desired product (1.65 g, Yield 80%). LCMS (m/z): 197.0 (M+1). The mixture was cooled concentrated in vacuo diluted with ethyl acetate and aq. NaHCO3 The mixture was extracted further with ethyl acetate the combined organic layers dried concentrated to give the crude product which was purified by column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromo-2-nitroaniline (2 g, 9.2 mmol), Fe powder (1.54 g, 27.6 mmol) and NH4Cl (4.8 g, 52 mmol) in EtOH and H2O was stirred under reflux for 1 h. The mixture was cooled to room temperature and filtered. The filtrate was diluted water extracted with ethyl acetate and the combined organic layers were dried and concentrated in vacuum to give the crude desired product (1.7 g, Yield 85%). This crude was used in the next step without further purification. under reflux for 1 h filtered extracted with ethyl acetate the combined organic layers were dried concentrated in vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (5-Bromo-1H-benzoimidazol-2-yl)-methanol was prepared by the same procedure as [5-bromo-1-(3-methyl-butyl)-1H-benzoimidazol-2-yl]-methanol, starting with 3-bromophenylenediamine.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (5-Bromo-1H-benzoimidazol-2-yl)-methanol was prepared by the same procedure as [5-bromo-1-(3-methyl-butyl)-1H-benzoimidazol-2-yl]-methanol, starting with 3-bromophenylenediamine.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,2-diamino-3-bromobenzene (2.00 g, 10.7 mmol) in formic acid (10 mL) was stirred at 100° C. for 1 hour. The pH of the mixture was adjusted to 14 by the addition of 4 M sodium hydroxide solution, precipitating the product as a solid. This was separated by filtration, washed with water and air-dried affording the product as an off-white solid. A further crop of equally pure material precipitated from the filtrate upon standing at room temperature for a few days. Total yield=1.98 g, 94%. 1H NMR (500 MHz, d6-DMSO): δ 12.83 (1H, s), 8.30 (1H, s), 7.58 (1H, d, J=7.9 Hz), 7.41 (1H, d, J=7.1 Hz), 7.14 (1H, t, J=7.8 Hz); m/z (ES+) 197, 199 [MH+]. precipitating the product as a solid This was separated by filtration washed with water air-dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,2-diamino-3-bromobenzene (2.00 g, 10.7 mmol) in formic acid (10 mL) was stirred at 100° C. for 1 hour. The pH of the mixture was adjusted to 14 by the addition of 4 M sodium hydroxide solution, precipitating the product as a solid. This was separated by filtration, washed with water and air-dried affording the product as an off-white solid. A further crop of equally pure material precipitated from the filtrate upon standing at room temperature for a few days. Total yield=1.98 g, 94%. 1H NMR (500 MHz, d6-DMSO): δ 12.83 (1H, s), 8.30 (1H, s), 7.58 (1H, d, J=7.9 Hz), 7.41 (1H, d, J=7.1 Hz), 7.14 (1H, t, J=7.8 Hz); m/z (ES+) 197, 199 [MH+]. precipitating the product as a solid This was separated by filtration washed with water air-dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring slurry of tin(II) chloride dihyrate (11.8 g, 52.3 mmol) in conc. hydrochloric acid (55 mL) was added 2-bromo-6-nitroaniline (2.84 g, 13.1 mmol), and the resulting mixture was stirred at room temperature for 5 minutes—an exotherm was observed. The mixture was then stirred at reflux for 30 minutes. After cooling to room temperature, the slurry was poured onto crushed ice (200 mL), and the pH was adjusted to 14 by the addition of sodium hydroxide pellets. The resulting mixture was washed with diethyl ether (5×100 mL), then the combined organic layers were dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on a Biotage SP1 apparatus, on a 40S silica gel column, eluting with 5% to 50% ethyl acetate in dichloromethane, yielding the product as a yellow-brown oil, which solidified upon standing (2.02 g, 87%) 1H NMR (400 MHz, CDCl3): δ 6.97 (1H, dd, J=1.4, 8.0 Hz), 6.64 (1H, dd, J=1.4, 7.8 Hz), 6.56 (1H, t, J=7.9 Hz), 3.61 (3H, s); m/z (ES+) 187, 189 [MH+]. The mixture was then stirred at reflux for 30 minutes After cooling to room temperature the slurry was poured The resulting mixture was washed with diethyl ether (5×100 mL) the combined organic layers were dried (MgSO4) concentrated in vacuo The crude product was purified by chromatography on a Biotage SP1 apparatus, on a 40S silica gel column eluting with 5% to 50% ethyl acetate in dichloromethane