(2-methylsulfanylphenyl)methanamine

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: A solution of 2-(methylthio)benzonitrile (29.8 g) in dry ether (150 ml ) was added dropwise to a stirred suspension of lithium aluminium hydride (11.6 g) in dry ether (360 ml) under nitrogen. A thick gum formed which was dissolved by the addition of dry THF (100 ml). The mixture was stirred at room temperature for 2 hours, Water (12 ml) was then carefully added followed by a 15% aqueous solution of sodium hydroxide (36 ml) and more water (12 ml). The mixture, was filtered, the filtrate washed with water, dried and evaporated in vacuo. The residue was distilled in vacuo to give a colourless oil. Yield=20.9 g. A thick gum formed which The mixture, was filtered the filtrate washed with water dried evaporated in vacuo The residue was distilled in vacuo to give a colourless oil

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-methyl-3-(2-oxo-3-phenoxy-2H-pyrazin-1-yl)-benzoic acid, methyl ester (Example 128a, 111 mg), 2-(methylthio)-benzenemethanamine (100 mg) and tetrahydrofuran (1 mL) was heated within a microwave for 5 h at 120° C. before being cooled to room temperature. Cyclopropylamine (0.2 mL) was added followed by addition of cyclopentylmagnesium bromide (2M in diethyl ether, 0.8 mL). The mixture was stirred for 10 min., quenched with sat. NH4Cl and extracted into ethyl acetate. The organic phase was concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound as a solid (39 mg). before being cooled to room temperature quenched with sat. NH4Cl extracted into ethyl acetate The organic phase was concentrated in vacuo Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

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

Procedure: To a 25 mL round bottomed flask with a stirring bar, reflux condenser and a nitrogen inlet was added 5-bromo-8-hydroxy-[1,6]naphthyridine-7-carboxylic acid methyl ester (0.511 g, 1.81 mmol) dry toluene (12.5 mL) and 2-methylthiobenzylamine (0.346 g, 2.26 mmol). This mixture was heated at reflux for 24 h. The mixture was cooled to ambient temperature and the toluene was removed in vacuo. The residue was triturated with a little Et2O/hexane, collected on a frit and dried in vacuo to give 8-hydroxy-5-bromo-[1,6]naphthyridine-7-carboxylic acid 2-methylsulfanylbenzylamide as a crystalline solid. To a 25 mL round bottomed flask with a stirring bar, reflux condenser and a nitrogen inlet This mixture was heated at reflux for 24 h the toluene was removed in vacuo The residue was triturated with a little Et2O/hexane collected on a frit dried in vacuo

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

Procedure: To a 25 mL round bottomed flask with a stirring bar, reflux condenser and a nitrogen inlet was added 5-bromo-8-hydroxy-[1,6]naphthyridine-7-carboxylic acid methyl ester (0.511 g, 1.81 mmol) dry toluene (12.5 mL) and 2-methylthiobenzylamine (0.346 g, 2.26 mmol). This mixture was heated at reflux for 24 h. The mixture was cooled to ambient temperature and the toluene was removed in vacuo. The residue was triturated with a little Et2O/hexane, collected on a frit and dried in vacuo to give 8-hydroxy-5-bromo-[1,6]naphthyridine-7-carboxylic acid 2-methylsulfanylbenzylamide as a crystalline solid. To a 25 mL round bottomed flask with a stirring bar, reflux condenser and a nitrogen inlet This mixture was heated at reflux for 24 h the toluene was removed in vacuo The residue was triturated with a little Et2O/hexane collected on a frit dried in vacuo

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

Procedure: A solution of 2-(methylthio)benzonitrile (29.8 g) in dry ether (150 ml ) was added dropwise to a stirred suspension of lithium aluminium hydride (11.6 g) in dry ether (360 ml) under nitrogen. A thick gum formed which was dissolved by the addition of dry THF (100 ml). The mixture was stirred at room temperature for 2 hours, Water (12 ml) was then carefully added followed by a 15% aqueous solution of sodium hydroxide (36 ml) and more water (12 ml). The mixture, was filtered, the filtrate washed with water, dried and evaporated in vacuo. The residue was distilled in vacuo to give a colourless oil. Yield=20.9 g. A thick gum formed which The mixture, was filtered the filtrate washed with water dried evaporated in vacuo The residue was distilled in vacuo to give a colourless oil

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-methyl-3-(2-oxo-3-phenoxy-2H-pyrazin-1-yl)-benzoic acid, methyl ester (Example 128a, 111 mg), 2-(methylthio)-benzenemethanamine (100 mg) and tetrahydrofuran (1 mL) was heated within a microwave for 5 h at 120° C. before being cooled to room temperature. Cyclopropylamine (0.2 mL) was added followed by addition of cyclopentylmagnesium bromide (2M in diethyl ether, 0.8 mL). The mixture was stirred for 10 min., quenched with sat. NH4Cl and extracted into ethyl acetate. The organic phase was concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound as a solid (39 mg). before being cooled to room temperature quenched with sat. NH4Cl extracted into ethyl acetate The organic phase was concentrated in vacuo Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-methyl-3-(2-oxo-3-phenoxy-2H-pyrazin-1-yl)-benzoic acid, methyl ester (Example 128a, 111 mg), 2-(methylthio)-benzenemethanamine (100 mg) and tetrahydrofuran (1 mL) was heated within a microwave for 5 h at 120° C. before being cooled to room temperature. Cyclopropylamine (0.2 mL) was added followed by addition of cyclopentylmagnesium bromide (2M in diethyl ether, 0.8 mL). The mixture was stirred for 10 min., quenched with sat. NH4Cl and extracted into ethyl acetate. The organic phase was concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound as a solid (39 mg). before being cooled to room temperature quenched with sat. NH4Cl extracted into ethyl acetate The organic phase was concentrated in vacuo Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

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