ethyl 2-imino-2-methylsulfanylacetate

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-4-bromoacetophenone hydrochloride (4.0 g, 16.0 mmol), sodium acetate (6.1 g, 90.0 mmol), acetic acid (4.6 mL, 80.0 mmol) and ethyl 2-imino-2-(methylthio)acetate (7.7 g, 32.0 mmol) in dioxane (40 mL) was stirred at 95° C. overnight. The reaction mixture was carefully neutralized with saturated NaHCO3 solution and extracted with ethyl acetate. The organic solution was dried over sodium sulfate and concentrated. Purification by silica gel column chromatography (ethyl acetate:hexanes 1:1) afforded ethyl 4-(4-bromophenyl)-1H-imidazole-2-carboxylate (3.53 g, 75.0%). MS (EI) for C12H11BrN2O2: 296 (MH+). extracted with ethyl acetate The organic solution was dried over sodium sulfate concentrated Purification by silica gel column chromatography (ethyl acetate:hexanes 1:1)

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-4-bromoacetophenone hydrochloride (4.0 g, 16.0 mmol), sodium acetate (6.1 g, 90.0 mmol), acetic acid (4.6 mL, 80.0 mmol) and ethyl 2-imino-2-(methylthio)acetate (7.7 g, 32.0 mmol) in dioxane (40 mL) was stirred at 95° C. overnight. The reaction mixture was carefully neutralized with saturated NaHCO3 solution and extracted with ethyl acetate. The organic solution was dried over sodium sulfate and concentrated. Purification by silica gel column chromatography (ethyl acetate:hexanes 1:1) afforded ethyl 4-(4-bromophenyl)-1H-imidazole-2-carboxylate (3.53 g, 75.0%). MS (EI) for C12H11BrN2O2: 296 (MH+). extracted with ethyl acetate The organic solution was dried over sodium sulfate concentrated Purification by silica gel column chromatography (ethyl acetate:hexanes 1:1)

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-4-bromoacetophenone hydrochloride (4.0 g, 16.0 mmol), sodium acetate (6.1 g, 90.0 mmol), acetic acid (4.6 mL, 80.0 mmol) and ethyl 2-imino-2-(methylthio)acetate (7.7 g, 32.0 mmol) in dioxane (40 mL) was stirred at 95° C. overnight. The reaction mixture was carefully neutralized with saturated NaHCO3 solution and extracted with ethyl acetate. The organic solution was dried over sodium sulfate and concentrated. Purification by silica gel column chromatography (ethyl acetate:hexanes 1:1) afforded ethyl 4-(4-bromophenyl)-1H-imidazole-2-carboxylate (3.53 g, 75.0%). MS (EI) for C12H11BrN2O2: 296 (MH+). extracted with ethyl acetate The organic solution was dried over sodium sulfate concentrated Purification by silica gel column chromatography (ethyl acetate:hexanes 1:1)

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

Procedure: A solution of 0.90 g (5.45 mmol) of 2-amino-3-(2-fluorophenyl)propanenitrile from example 8A and 2.20 g (9.27 mmol) of ethyl imino(methylthio)acetate [D. Catarzi et al., J. Med. Chem. 1995, 38, 2196-2201] in 10 ml of dioxane is stirred at RT for two days. The solution is then concentrated in vacuo, and the residue is purified by preparative HPLC. 770 mg (54% of theory) of the desired product are obtained. The solution is then concentrated in vacuo the residue is purified by preparative HPLC

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-4-bromoacetophenone hydrochloride (4.0 g, 16.0 mmol), sodium acetate (6.1 g, 90.0 mmol), acetic acid (4.6 mL, 80.0 mmol) and ethyl 2-imino-2-(methylthio)acetate (7.7 g, 32.0 mmol) in dioxane (40 mL) was stirred at 95° C. overnight. The reaction mixture was carefully neutralized with saturated NaHCO3 solution and extracted with ethyl acetate. The organic solution was dried over sodium sulfate and concentrated. Purification by silica gel column chromatography (ethyl acetate:hexanes 1:1) afforded ethyl 4-(4-bromophenyl)-1H-imidazole-2-carboxylate (3.53 g, 75.0%). MS (EI) for C12H11BrN2O2: 296 (MH+). extracted with ethyl acetate The organic solution was dried over sodium sulfate concentrated Purification by silica gel column chromatography (ethyl acetate:hexanes 1:1)