2-phenylethanamine;hydrochloride

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

Procedure: Into a 10-mL sealed tube, was placed methyl 3-bromo-2-phenylquinoxaline-6-carboxylate (150 mg, 0.44 mmol, 1.00 equiv), 2-phenylethanamine hydrochloride (207.8 mg, 1.32 mmol, 3.00 equiv), potassium carbonate (304.4 mg, 2.21 mmol, 5.00 equiv), N,N-dimethylformamide (2 mL). The resulting solution was stirred overnight at 100° C. in an oil bath. The reaction was then quenched by the addition of 20 mL of water. The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:50). This resulted in 120 mg (71%) of methyl 3-(phenethylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid. Into a 10-mL sealed tube The reaction was then quenched by the addition of 20 mL of water The resulting solution was extracted with 3×50 mL of ethyl acetate The organic layer was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 120 mg (71%) of methyl 3-(phenethylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of phenylethylamine hydrochloride (2.88 g, 0.018 mol) and 2-bromo-N-tert-butyloxycarbonylethylamine (4.1 g, 0.018 mmol) in DMF (50 mL), containing K2CO3 (5.0 g, 0.036 mol), was heated at 60° C. for 4 h. The solution was filtered, evaporated and the residue partitioned between CH2Cl2 (2×100 mL) and water (100 mL). The combined organic layers were dried (Na2SO4) and evaporated. The residue was chromatographed on silica gel, eluting with CH2Cl2 :MeOH (90:10), to afford the title compound (1.44 g, 30%) as a colourless oil. 1H NMR (250 MHz, CDCl3) δ 1.44 (9H, s), 2.74 (2H, t, J=6.0Hz), 2.79 (2H, m), 2.88 (2H, m), 3.19 (2H, m), 4.87 (1H, br s), 7.19-7.22 (3H, m), 7.26-7.31 (2H, m). MS (ES+) (265, M+1). The solution was filtered evaporated the residue partitioned between CH2Cl2 (2×100 mL) and water (100 mL) The combined organic layers were dried (Na2SO4) evaporated The residue was chromatographed on silica gel eluting with CH2Cl2 :MeOH (90:10)

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

Procedure: 37.6 ml cyclohexanone, 5.75 g paraformaldehyde, 38 ml glacial acetic acid and 30.2 g benzylmethylamine hydrochloride were heated at 105° C. (bath temperature) for 25 minutes, while stirring, the mixture was concentrated in vacuo (10 mbar), the residue was taken up in 100 ml 2-butanone and the mixture was concentrated again in vacuo. The residue was heated under reflux with 150 ml 2-butanone. After cooling to room temperature, the mixture was filtered and the residue on the filter was dried in vacuo. 36 g 2-[(benzylmethylamino)methyl]cyclohexanone were obtained. the mixture was concentrated in vacuo (10 mbar) the mixture was concentrated again in vacuo The residue was heated under reflux with 150 ml 2-butanone the mixture was filtered the residue on the filter was dried in vacuo

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

Procedure: 37.6 ml cyclohexanone, 5.75 g paraformaldehyde, 38 ml glacial acetic acid and 30.2 g benzylmethylamine hydrochloride were heated at 105° C. (bath temperature) for 25 minutes, while stirring, the mixture was concentrated in vacuo (10 mbar), the residue was taken up in 100 ml 2-butanone and the mixture was concentrated again in vacuo. The residue was heated under reflux with 150 ml 2-butanone. After cooling to room temperature, the mixture was filtered and the residue on the filter was dried in vacuo. 36 g 2-[(benzylmethylamino)methyl]cyclohexanone were obtained. the mixture was concentrated in vacuo (10 mbar) the mixture was concentrated again in vacuo The residue was heated under reflux with 150 ml 2-butanone the mixture was filtered the residue on the filter was dried in vacuo

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

Procedure: A solution of 1.425 g. (5 millimols) diisopropyl N-(2-phenylethyl)-phosphoramidate in 20 ml. diisopropyl ether saturated with hydrogen chloride is stirred overnight at ambient temperature. The precipitate of 2-phenylethylamine hydrochloride formed is filtered off, washed with diisopropyl ether and then dried in vacuo to give 0.75 g. (yield: 95%) of a crystalline solid, the physical and spectral characteristics of which are identical to those of the compound prepared in Example 2.

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

Procedure: A mixture comprising 3-methoxy-4-nitrobenzonitrile (1 g, 5.6 mmol), phenethylamine hydrochloride (1.8 g, 11.2 mmol), 50% sodium hydroxide (0.9 g, 11.2 mmol) and DMSO (3 mL) was heated at 100° C. for 3.5 hours, cooled and poured into a solution of 1N hydrochloric acid (200 mL, 0° C.). The mixture was stirred for 20 minutes to give a precipitate. The precipitate was collected and recrystallized from hot ethanol to provide 4-nitro-3-phenethylaminobenzonitrile (0.78 g, 2.9 mmol) as orange crystals. MS (CI), Calculated for C15H13N3O2, 267.3, Found (MH+): 282. A mixture comprising 4-nitro-3-phenethylaminobenzonitrile (0.75 g, 2.8 mmol), palladium on carbon (100 mg) and 1:1 methanol/THF (100 mL) was hydrogenated under 1 atm for 3 hours, filtered and concentrated under reduced pressure to provide 4-amino-3-phenethylaminobenzonitrile (0.68 g, 2.8 mmol) as a tan solid. cooled to give a precipitate The precipitate was collected recrystallized from hot ethanol

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

Procedure: Phenethylamine hydrochloride (4.7 g), 2.7 g of paraformaldehyde and 4.6 g of 6-methyl-1,2,3,4,7,8,9,10-octahydro-benzo[f]quinoline-3,10-dione are added to 200 ml of ethanol, and the mixture is stirred under reflux for 2 days. The reaction mixture is then cooled, and the precipitated crystals are collected by filtration and recrystallized from 60% ethanol to give 2.0 g of 6-methyl-1,2,3,4,7,8,9,10-octahydro-9-phenethylaminomethylbenzo[f]quinoline-3,10-dione hydrochloride as colorless needles, melting at 190°-192° C. under reflux for 2 days The reaction mixture is then cooled the precipitated crystals are collected by filtration recrystallized from 60% ethanol

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

Procedure: Phenethylamine hydrochloride (257 grams, 1.63 moles) and ammonium thiocyanate (123.6 grams, 1.63 moles) were heated to 160° C. in 340 ml bromobenzene under nitrogen. After heating for 90 minutes, the mixture was cooled to room temperature and then to 5° C. This procedure was repeated with a further batch of 257 grams of phenethylamine hydrochloride. The combined solids obtained in the above reaction were stirred in 1.5 l water and filtered. Recrystallization from isopropyl alcohol yielded 261.5 grams (45%) N-phenethylthiourea, m.p. 132°-134°. After heating for 90 minutes to 5° C The combined solids obtained in the above reaction filtered Recrystallization from isopropyl alcohol

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

Procedure: 5-Chloro-2-methoxybenzoyl chloride (15g.), dissolved in benzene, was added slowly to a solution of phenethylamine (18 g.) in benzene. Phenethylamine hydrochloride formed was filtered off, and the benzene removed from the filtrate. The residual oil was distilled to give an oil (19.4 g., 90%) b.p. 205° at 0.2 mm., which crystallized on standing m.p. 60°-63°.

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

Procedure: Into a 10-mL sealed tube, was placed methyl 3-bromo-2-phenylquinoxaline-6-carboxylate (150 mg, 0.44 mmol, 1.00 equiv), 2-phenylethanamine hydrochloride (207.8 mg, 1.32 mmol, 3.00 equiv), potassium carbonate (304.4 mg, 2.21 mmol, 5.00 equiv), N,N-dimethylformamide (2 mL). The resulting solution was stirred overnight at 100° C. in an oil bath. The reaction was then quenched by the addition of 20 mL of water. The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:50). This resulted in 120 mg (71%) of methyl 3-(phenethylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid. Into a 10-mL sealed tube The reaction was then quenched by the addition of 20 mL of water The resulting solution was extracted with 3×50 mL of ethyl acetate The organic layer was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 120 mg (71%) of methyl 3-(phenethylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid

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

Procedure: 87.5 g (0.55 mole) of N-benzylmethylamine hydrochloride, 84 g (1.0 mole) of cyclopentanone, 45 g of paraformaldehyde (1.5 moles of formaldehyde) and 500 ml of ethanol are refluxed for one hour whilst stirring, during which solution occurs. After the solution has cooled, the solvent is distilled off under reduced pressure, the oily residue is dissolved in 100 ml of isopropanol and 500 ml of ethyl acetate are then added, whereupon the product crystallizes out after some time. After the solution has cooled the solvent is distilled off under reduced pressure the oily residue is dissolved in 100 ml of isopropanol 500 ml of ethyl acetate are then added, whereupon the product crystallizes out after some time

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

Procedure: Into a 10-mL sealed tube, was placed methyl 3-bromo-2-phenylquinoxaline-6-carboxylate (150 mg, 0.44 mmol, 1.00 equiv), 2-phenylethanamine hydrochloride (207.8 mg, 1.32 mmol, 3.00 equiv), potassium carbonate (304.4 mg, 2.21 mmol, 5.00 equiv), N,N-dimethylformamide (2 mL). The resulting solution was stirred overnight at 100° C. in an oil bath. The reaction was then quenched by the addition of 20 mL of water. The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:50). This resulted in 120 mg (71%) of methyl 3-(phenethylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid. Into a 10-mL sealed tube The reaction was then quenched by the addition of 20 mL of water The resulting solution was extracted with 3×50 mL of ethyl acetate The organic layer was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 120 mg (71%) of methyl 3-(phenethylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid