3-chlorobenzene-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:

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: Cyanogen bromide was added to a solution of 3-chlorobenzene-1,2-diamine (0.81 g, 0.570 mmol) in acetonitrile (10 mL) and water (2 ml) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 14 hours. The reaction was quenched with saturated aqueous sodium hydrogen carbonate (50 ml) and shaken. The resulting solid was filtered off, was washed with water and dried at reduced pressure to 0.49 g of 4-chloro-1H-benzo[d]imidazol-2-amine (yield, 49%). MS (EI): 168 (MH+). The reaction was quenched with saturated aqueous sodium hydrogen carbonate (50 ml) shaken The resulting solid was filtered off was washed with water dried at reduced pressure to 0.49 g of 4-chloro-1H-benzo[d]imidazol-2-amine (yield, 49%)

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

Procedure: A solution of 2-chloro-6-nitroaniline (1.0 g, 5.81 mmol, commercially available from Apollo International) in methanol (20 mL) was passed through the H-Cube® (Thales Nanotechnology Inc.) operating at 40 bars and ambient temperature with a flow rate of 1 mL/min. The H-Cube® was equipped with a 10% Pd/C cartridge (Catcart™). The reaction mixture was collected and concentrated after being exposed to the hydrogenation conditions. The crude 3-chlorobenzene-1,2-diamine was carried on without further purification. MS (EI): 145 (MH+). operating at 40 bars and ambient temperature with a flow rate of 1 mL/min The reaction mixture was collected concentrated The crude 3-chlorobenzene-1,2-diamine was carried on without further purification

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-chloro-benzene-1,2-diamine (0.820 g, 5.75 mmol) and THF (25 mL), was added carbonyl diimidazole (1.12 g, 6.90 mmol) at 0° C. The mixture was stirred for 16 h and allowed to warm to 23° C. A solution of 1M aqueous HCl (25 mL) was added to the reaction mixture at 0° C., followed by water (100 mL) and the mixture was stirred for 1 h. The precipitated solid was filtered and dried under high vacuum for 18 h to yield the titled compound, which was used in the next step without further purification (0.800 g, 83%). MS (ESI/CI): mass calcd. for C7H6ClN2O, 168.0; m/z found, 169.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6): 11.13 (s, 1H), 10.88 (s, 1H), 7.00-6.86 (m, 3H). the mixture was stirred for 1 h The precipitated solid was filtered dried under high vacuum for 18 h

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-chloro-2-nitro-phenylamine (1.73 g, 10.0 mmol), NH4Cl (2.68 g, 50.0 mmol), acetone (40 mL) and water (10 mL), was added zinc powder portion-wise (three equal portions over 5 minutes) (3.26 g, 50.0 mmol) at 0° C. The mixture was stirred for 2 h then warmed to 23° C. The mixture was filtered through Celite® and the solvents were concentrated under reduced pressure. The mixture was re-dissolved in EtOAc/DCM and filtered a second time through Celite® and the solvents were evaporated. The crude mixture was diluted with EtOAc (100 mL), washed with brine (40 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (10-50% EtOAc/hexanes) to yield the titled compound (1.00 g, 70%). MS (ESI/CI): mass calcd. for C6H7ClN2, 142.0; m/z found, 143.1 [M+H]+. 1H NMR (500 MHz, CDCl3): 6.86-6.78 (m, 1H), 6.65-6.58 (m, 2H), 3.74 (br s, 2H), 3.46 (br s, 2H). The mixture was filtered through Celite® the solvents were concentrated under reduced pressure The mixture was re-dissolved in EtOAc/DCM filtered a second time through Celite® the solvents were evaporated The crude mixture was diluted with EtOAc (100 mL) washed with brine (40 mL) dried filtered concentrated under reduced pressure The residue was purified (FCC) (10-50% EtOAc/hexanes)

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

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

Procedure: 10.5 g (73.6 mmol) of 3-chloro-1,2-phenylenediamine and 12.8 g (73.5 mmol) of diethyl ketomalonate were dissolved in ethanol, and the solution was heated to reflux for 3 hours. While heating to reflux, ethanol was added thereto until precipitated crystals dissolved. The reaction mixture was cooled to room temperature, and then precipitated crystals were separated by filtration. The filter cake was washed with cold ethanol, and then dried, to obtain 10.5 g (yield: 51%) of ethyl 5-chloro-2-oxo-1,2-dihydroquinoxaline-3-carboxylate as pale yellow acicular crystals. the solution was heated to reflux for 3 hours While heating to reflux until precipitated crystals dissolved precipitated crystals were separated by filtration The filter cake was washed with cold ethanol dried