2-(2-bromophenyl)ethanamine

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: 5 g of 2-(2-bromophenyl)ethanamine and 10 g of potassium carbonate in 30 cm3 of anhydrous tetrahydrofuran are stirred under an inert atmosphere at a temperature close to 10° C. 2.5 cm3 of methyl chlorocarbonate in solution in 10 cm3 of tetrahydrofuran are poured into the reaction mixture. After returning to a temperature close to 20° C., the reaction mixture is heated for 2 h at the reflux of the solvent. The potassium carbonate is filtered and washed with tetrahydrofuran. The filtrate is concentrated using a rotary evaporator under reduced pressure (5 kPa). 3.43 g of methyl[2-(2-bromophenyl)ethyl]carbamate are obtained in the form of a colorless thick oil close to 10° C close to 20° C. the reaction mixture is heated for 2 h at the reflux of the solvent The potassium carbonate is filtered washed with tetrahydrofuran The filtrate is concentrated a rotary evaporator under reduced pressure (5 kPa)

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

Procedure: 10 g of 2-bromophenethylamine and 5.71 g of 4-heptanone are dissolved in 250 cm3 of 1,2-dichloroethane at a temperature close to 20° C. 14.84 g of sodium triacetoxyborohydride and 2.9 cm3 of glacial acetic acid are added to the reaction medium. Stirring is continued for 20 h. 300 cm3 of 1M sodium hydroxide are added to the reaction medium. The aqueous phase is extracted with 3 lots of 100 cm3 of ethyl acetate. The organic phases are combined and washed with 4 lots of 100 cm3 of water then 100 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated using a rotary evaporator under reduced pressure (5 kPa). The yellow liquid obtained is purified by flash chromatography over silica (column: 400 g; particle size: 20-40 μm, spherical; flow rate: 30 cm3/min; eluent: 100% heptane to 70% ethyl acetate/30% heptane gradient). After concentrating the fractions under reduced pressure, 17.33 g of N-[2-(2-bromophenyl)ethyl]heptan-4-amine are obtained. close to 20° C The aqueous phase is extracted with 3 lots of 100 cm3 of ethyl acetate washed with 4 lots of 100 cm3 of water 100 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate concentrated a rotary evaporator under reduced pressure (5 kPa) The yellow liquid obtained is purified by flash chromatography over silica (column: 400 g; particle size: 20-40 μm, spherical; flow rate: 30 cm3/min; eluent: 100% heptane to 70% ethyl acetate/30% heptane gradient) After concentrating the fractions under reduced pressure, 17.33 g of N-[2-(2-bromophenyl)ethyl]heptan-4-amine are obtained

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

Procedure: To the styrene of Step 1 (0.310 g, 1.3 mmol) in 5 mL of THF was added 1 M LiAlH4 solution in THF (5.2 mL, 5.2 mmol) at 0° C. The solution was stirred for 1 hour. A concentrated KHSO4 solution was added dropwise to destroy the excess of LiAlH4. The solution was filtered over celite and the filtrate concentrated in vacuo to give a yellow oil; 150 mg (58%). to destroy the excess of LiAlH4 The solution was filtered over celite the filtrate concentrated in vacuo to give a yellow oil

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

Procedure: 4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1) (200 mg, 0.531 mmol) was diluted with DCM (3 mL) followed by the addition of oxalyl chloride in DCM (2M) (292 μl, 0.584 mmol) and DMF (1 drop). After stirring for 20 minutes, 2-(2-bromophenyl)ethanamine (117 mg, 0.584 mmol) and DIEA (203 μl, 1.17 mmol) were added and the reaction was stirred at ambient temperature for 12 hours. The reaction was loaded directly onto a biotage 25 cartridge and eluted with 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes to yield ethyl 7-(4-(2-bromophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (268 mg, 0.480 mmol, 90.3% yield). the reaction was stirred at ambient temperature for 12 hours eluted with 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes

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

Procedure: 4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1) (200 mg, 0.531 mmol) was diluted with DCM (3 mL) followed by the addition of oxalyl chloride in DCM (2M) (292 μl, 0.584 mmol) and DMF (1 drop). After stirring for 20 minutes, 2-(2-bromophenyl)ethanamine (117 mg, 0.584 mmol) and DIEA (203 μl, 1.17 mmol) were added and the reaction was stirred at ambient temperature for 12 hours. The reaction was loaded directly onto a biotage 25 cartridge and eluted with 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes to yield ethyl 7-(4-(2-bromophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (268 mg, 0.480 mmol, 90.3% yield). the reaction was stirred at ambient temperature for 12 hours eluted with 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes

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

Procedure: 4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1) (200 mg, 0.531 mmol) was diluted with DCM (3 mL) followed by the addition of oxalyl chloride in DCM (2M) (292 μl, 0.584 mmol) and DMF (1 drop). After stirring for 20 minutes, 2-(2-bromophenyl)ethanamine (117 mg, 0.584 mmol) and DIEA (203 μl, 1.17 mmol) were added and the reaction was stirred at ambient temperature for 12 hours. The reaction was loaded directly onto a biotage 25 cartridge and eluted with 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes to yield ethyl 7-(4-(2-bromophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (268 mg, 0.480 mmol, 90.3% yield). the reaction was stirred at ambient temperature for 12 hours eluted with 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes

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

Procedure: In close analogy to the procedure described above, 2-(2-Bromo-phenyl)-ethylamine is reacted with acetic anhydride to provide the title compound.

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

Procedure: In close analogy to the procedure described above, 2-(2-Bromo-phenyl)-ethylamine is reacted with acetic anhydride to provide the title compound.

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

Procedure: Into a 10-mL sealed tube, was placed methyl 3-chloro-2-phenylquinoxaline-6-carboxylate (150 mg, 0.50 mmol, 1.00 equiv), 2-(2-bromophenyl)ethanamine (300.5 mg, 1.51 mmol, 3.00 equiv), potassium carbonate (347.3 mg, 2.52 mmol, 5.00 equiv), toluene/DMSO (5/1 mL). The resulting solution was stirred for overnight at 100° C. in an oil bath. The resulting mixture was concentrated under vacuum and applied onto a silica gel column with ethyl acetate/petroleum ether (1:50). This resulted in 110 mg (47%) of methyl 3-(2-bromophenethylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid. Into a 10-mL sealed tube The resulting mixture was concentrated under vacuum This resulted in 110 mg (47%) of methyl 3-(2-bromophenethylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid