(2S)-1-N,1-N-dimethyl-3-phenylpropane-1,2-diamine

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

Procedure: The title compound was prepared by a similar method to preparation 18 from N-[(2S)-2-amino-3-phenylpropyl]-N,N-dimethylamine (190 mg, 1.07 mmol; prepared as described in Chem. Pharm. Bull. 1970, 18,1731-1736) and benzyl 2-[3,5-dichloro-2-methyl-6-oxo-1(6H)-pyrazinyl]acetate (preparation 17) (361 mg, 1.10 mmol). The crude product was purified by chromatography (SiO2; gradient elution 100% hexane; 80:20 hexane:ethyl acetate; 60:40 hexane:ethyl acetate; 40:60 hexane:ethyl acetate; 20:80 hexane:ethyl acetate) to give the desired product (yellow solid, 260 mg, 50%). 1H NMR (CDCl3) δ 2.20 (m, 9H), 2.30 (m, 1H), 2.20 (m, 1H), 2.85 (m, 1H), 3.10 (m, 1H), 4.25 (m, 1H), 4.80 (s, 2H), 5.20 (s, 2H), 6.20 (m, 1H), 7.20 (m, 5H), 7.35 (m, 5H). LRMS m/z=469.2, 471.3 (M+1)+. The crude product was purified by chromatography (SiO2; gradient elution 100% hexane; 80:20 hexane:ethyl acetate; 60:40 hexane:ethyl acetate; 40:60 hexane:ethyl acetate; 20:80 hexane:ethyl acetate)

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

Procedure: The title compound was prepared by a similar method to preparation 18 from N-[(2S)-2-amino-3-phenylpropyl]-N,N-dimethylamine (190 mg, 1.07 mmol; prepared as described in Chem. Pharm. Bull. 1970, 18, 1731-1736) and benzyl 2-[3,5-dichloro-2-methyl-6-oxo-1(6H)-pyrazinyl]acetate (preparation 17) (361 mg, 1.10 mmol). The crude product was purified by chromatography (SiO2; gradient elution 100% hexane; 80:20 hexane:ethyl acetate; 60:40 hexane:ethyl acetate; 40:60 hexane:ethyl acetate; 20:80 hexane:ethyl acetate) to give the desired product (yellow solid, 260 mg, 50%). 1H NMR (CDCl3) δ 2.20 (m, 9H), 2.30 (m, 1H), 2.20 (m, 1H), 2.85 (m, 1H), 3.10 (m, 1H), 4.25 (m, 1H), 4.80 (s, 2H), 5.20 (s, 2H), 6.20 (m, 1H), 7.20 (m, 5H), 7.35 (m, 5H). LRMS m/z=469.2, 471.3 (M+1)+. The crude product was purified by chromatography (SiO2; gradient elution 100% hexane; 80:20 hexane:ethyl acetate; 60:40 hexane:ethyl acetate; 40:60 hexane:ethyl acetate; 20:80 hexane:ethyl acetate)

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

Procedure: To a solution of (S)-2-amino-N,N-dimethyl-3-phenyl-propionamide (1.0 g, 5.2 mmol) in tetrahydrofuran (10 mL) was added a solution of lithium aluminum hydride in tetrahydrofuran and toluene (3.5 M, 7.4 mL, 26 mmol) dropwise. The mixture was heated to reflux for 4 h after addition and then cooled. Ether (20 mL) was added. Ethyl acetate was added dropwise until all the lithium aluminum hydride was consumed. Sodium hydroxide (1M, 20 mL) was added and the mixture was stirred for 30 min. The mixture was extracted three times with ether. The combined organic extracts were washed with brine, dried over sodium sulfate and evaporated to give (S)—N1,N1-dimethyl-3-phenyl-propane-1,2-diamine (0.60 g, 65%) The mixture was heated to reflux for 4 h after addition cooled was consumed Sodium hydroxide (1M, 20 mL) was added The mixture was extracted three times with ether The combined organic extracts were washed with brine dried over sodium sulfate evaporated

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

Procedure: Lithium aluminum hydride (759 mg) was suspended in anhydrous ether (20 ml) with ice cooling in the nitrogen gas atmosphere and then a solution of (2S)-2-amino-N1,N1-dimethyl-3-phenylpropionamide (1.92 g) in anhydrous tetrahydrofuran (10 ml) was dropwise added to the resulting suspension. This mixture was stirred at room temperature for 1.5 hour. Ethyl acetate was gradually and dropwise added to the reaction liquid till the latter did not undergo foaming any more, with ice cooling. Then a 2N aqueous sodium hydroxide solution was added to the reaction liquid and the resulting mixture was extracted with chloroform. The organic phase thus obtained was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The resulting oily product was purified through the silica gel column chromatography to give the title compound (Reference Compound 1-1, 1.35 g). dropwise added to the reaction liquid till the latter the resulting mixture was extracted with chloroform The organic phase thus obtained was dried over anhydrous sodium sulfate concentrated under reduced pressure The resulting oily product was purified through the silica gel column chromatography

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

Procedure: The title compound was prepared by a similar method to preparation 18 from N-[(2S)-2-amino-3-phenylpropyl]-N,N-dimethylamine (190 mg, 1.07 mmol; prepared as described in Chem. Pharm. Bull. 1970, 18,1731-1736) and benzyl 2-[3,5-dichloro-2-methyl-6-oxo-1(6H)-pyrazinyl]acetate (preparation 17) (361 mg, 1.10 mmol). The crude product was purified by chromatography (SiO2; gradient elution 100% hexane; 80:20 hexane:ethyl acetate; 60:40 hexane:ethyl acetate; 40:60 hexane:ethyl acetate; 20:80 hexane:ethyl acetate) to give the desired product (yellow solid, 260 mg, 50%). 1H NMR (CDCl3) δ 2.20 (m, 9H), 2.30 (m, 1H), 2.20 (m, 1H), 2.85 (m, 1H), 3.10 (m, 1H), 4.25 (m, 1H), 4.80 (s, 2H), 5.20 (s, 2H), 6.20 (m, 1H), 7.20 (m, 5H), 7.35 (m, 5H). LRMS m/z=469.2, 471.3 (M+1)+. The crude product was purified by chromatography (SiO2; gradient elution 100% hexane; 80:20 hexane:ethyl acetate; 60:40 hexane:ethyl acetate; 40:60 hexane:ethyl acetate; 20:80 hexane:ethyl acetate)