2-amino-4-bromobenzaldehyde

Conditions: temp:22.01; pressure:0.00; stir:

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-4-bromobenzaldehyde (1 eq) and urea (14 eq) was heated to 180° C. in an oil bath under Argon for 1 h. Water was added to after cooling to ambient temperature. The solid was collected by filtration and air dried to give product in 95% yield. ES/MS m/z 225/227 (MH+). to after cooling to ambient temperature The solid was collected by filtration and air dried to give product in 95% yield

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

Procedure: To a 0.2M solution of 4-bromo-2-nitrobenzaldehyde in acetic acid and ethanol (v/v 1:1) solvent system was added iron powder. The reaction mixture was stirred at ambient temperature under Argon for 1.5 h and LCMS showed the reaction was complete. Insoluble solid was filtered off and the filtrate was concentrated in vacuum. Residue was diluted with ethyl acetate and was washed with saturated sodium bicarbonate, brine, dried over sodium sulfate and concentrated. Crude product was purified by Biotage using 15% ethyl acetate in hexane to give desired product in 38% yield. ES/MS m/z 200/202 (MH+). Insoluble solid was filtered off the filtrate was concentrated in vacuum Residue was diluted with ethyl acetate was washed with saturated sodium bicarbonate, brine dried over sodium sulfate concentrated Crude product was purified by Biotage

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

Procedure: A mixture of 3,3-diethoxypropanenitrile (1.80 mL, 12.00 mmol), 2-amino-4-bromobenzaldehyde (2 g, 10.00 mmol) and p-toluenesulfonic acid monohydrate (0.380 g, 2.000 mmol) in toluene (30 mL) was heated under reflux using Dean-Stark apparatus for 3 h. The reaction was cooled, evaporated under reduced pressure, and the residue was dissolved in a small amount of DMF, diluted with chloroform, and washed with aq. sodium bicarbonate solution. The aqueous layer was extracted with chloroform, and the combined extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo. Purification by flash chromatography (0-3% methanol in dichloromethane) followed by trituration in diethyl ether provided the title compound (1.75 g, 75%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.95 (dd, J=8.72, 1.89 Hz, 1 H) 8.08 (d, J=8.84 Hz, 1 H) 8.38 (d, J=2.02 Hz, 1 H) 9.13 (d, J=1.52 Hz, 1 H) 9.21 (d, 1 H). was heated under reflux for 3 h The reaction was cooled evaporated under reduced pressure the residue was dissolved in a small amount of DMF diluted with chloroform washed with aq. sodium bicarbonate solution The aqueous layer was extracted with chloroform the combined extracts were washed with brine dried (Na2SO4) concentrated in vacuo Purification by flash chromatography (0-3% methanol in dichloromethane)

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

Procedure: A mixture of 2-(2,2-diethoxyethyl)isoindoline-1,3-dione (3.16 g, 12.00 mmol), 2-amino-4-bromobenzaldehyde (2 g, 10.00 mmol) and p-toluenesulfonic acid monohydrate (1.902 g, 10.00 mmol) in toluene (60 mL) was heated under reflux using Dean-Stark apparatus overnight. A very dark/black solid precipitated overnight and was collected, washed with toluene and hexanes, then dissolved in chloroform fortified with DMF. The mixture was washed with aq. NaHCO3 solution (×2), ensuring any precipitate was dissolved in additional chloroform during separation. The organic layer was dried (sodium sulfate) and evaporated onto silica gel. Purification by flash chromatography (0-2% methanol in dichloromethane) afforded the title compound (1.6 g, 45%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.05 (d, 1 H), 8.57 (d, J=2.3 Hz, 1 H), 8.35 (d, J=1.8 Hz, 1 H), 8.11 (d, J=8.6 Hz, 1 H), 8.09-8.02 (m, 2 H), 8.02-7.93 (m, 2 H), 7.87 (dd, J=1.9, 8.7 Hz, 1 H). was heated under reflux Dean-Stark apparatus overnight A very dark/black solid precipitated overnight was collected washed with toluene and hexanes dissolved in chloroform The mixture was washed with aq. NaHCO3 solution (×2) was dissolved in additional chloroform during separation The organic layer was dried (sodium sulfate) evaporated onto silica gel Purification by flash chromatography (0-2% methanol in dichloromethane)

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

Procedure: A 1 L round bottom flask fitted with a stirbar, a Dean-Stark trap for solvents heavier than water, and a condenser was charged with 2-amino-4-bromobenzaldehyde (20 g, 100 mmol), sodium sulfate (71.0 g, 500 mmol), and p-toluenesulfonic acid monohydrate (4.75 g, 25.00 mmol). The solids were taken up in anhydrous chloroform (498 mL) and the suspension treated with 1-ethoxyprop-1-ene (14.39 mL, 130 mmol). The mixture was then heated to reflux with stirring overnight. The reaction mixture was cooled to room temperature and transferred to a 2 L separatory funnel. The solution was extracted twice with 200 mL saturated aq sodium bicarbonate and once with 200 mL water. The organic layer was isolated and the aqueous layers were combined and re-extracted twice with an additional 100 mL dichloromethane. The organics were then pooled, dried over sodium sulfate, filtered, and concentrated to a residue. The residue was purified by flash chromatography (0.2-1.9% methanol:dichloromethane). Fractions containing the desired material were pooled and concentrated to afford the title compound as a bright orange solid (5.603 g, 25.2 mmol, 25% yield). MS(ES)+ m/e 221.8 [M+H]+. A 1 L round bottom flask fitted with a stirbar The mixture was then heated to reflux transferred to a 2 L separatory funnel The solution was extracted twice with 200 mL saturated aq sodium bicarbonate and once with 200 mL water The organic layer was isolated re-extracted twice with an additional 100 mL dichloromethane dried over sodium sulfate filtered concentrated to a residue The residue was purified by flash chromatography (0.2-1.9% methanol:dichloromethane) Fractions containing the desired material concentrated

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

Procedure: A mixture of 3.3 g of 2-amino−4-bromobenzaldehyde, 3.3 g of 1-methoxy-3-phenylacetone, an aqueous potassium hydroxide solution (10 g of potassium hydroxide was dissolved in 10 ml of water) and 20 ml of ethanol was heated under stirring at 100° C. for 4 hours in a sealed tube. After cooling as it was, the reaction solution was poured into water and the mixture was extracted with diethyl ether. The organic phase was washed with brine and the solvent was removed. The residue was crystallized from hexane/ethyl acetate, to give 3.7 g of the target compound. After cooling as it the mixture was extracted with diethyl ether The organic phase was washed with brine the solvent was removed The residue was crystallized from hexane/ethyl acetate

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

Procedure: 16.1 ml of an aqueous 29% ammonia solution was added to a mixture of 5.0 g of 2-nitro-4-bromobenzaldehyde, 60.4 g of iron (II) sulfate heptahydrate, 200 ml of methanol, 100 ml of water and 335 μl of concentrated hydrochloric acid in an oil bath kept at 90° C., followed by heating under stirring for 10 minutes. After cooling as it was, insoluble matters were filtered through Celite and the filtrate was extracted with ethyl acetate. The organic phase was washed with brine and the solvent was removed, to give 3.9 g of the target compound. kept at 90° C. by heating After cooling as it insoluble matters were filtered through Celite the filtrate was extracted with ethyl acetate The organic phase was washed with brine the solvent was removed