methyl 4-amino-4-oxobutanoate

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: Using a method similar to the procedure described for the preparation of 4-[4-(2-nitro-phenyl)-oxazol-2-yl]-butyric acid methyl ester; reaction of 2-bromo-2′-nitroacetophenone (15.43 g, 63.2 mmol) with succinamic acid methyl ester (14.4 g, 110 mmol) gives 3-[4-(2-nitro-phenyl)-oxazol-2-yl]-propionic acid methyl ester (6.24 g, 36%). MS (ES): (M+1)+ 277.1 m/z.

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

Procedure: Using a method similar to the procedure described for the preparation of 4-[4-(2-nitro-phenyl)-oxazol-2-yl]-butyric acid methyl ester; reaction of 2-bromo-2′-nitroacetophenone (15.43 g, 63.2 mmol) with succinamic acid methyl ester (14.4 g, 110 mmol) gives 3-[4-(2-nitro-phenyl)-oxazol-2-yl]-propionic acid methyl ester (6.24 g, 36%). MS (ES): (M+1)+ 277.1 m/z.

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: Lawesson's reagent (2.6 g) was added to a toluene (10 ml) solution of methyl succinamate (1.7 g). The reaction mixture was heated under reflux for 4 hours, cooled, and then concentrated. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/1) to obtain the entitled compound (400 mg) as an oily substance. The reaction mixture was heated under reflux for 4 hours cooled concentrated The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/1)

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

Procedure: 8.9 mg of succinamic acid methyl ester, 25 mg of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and 12 μl diisopropyl-ethylamine were taken up in 0.4 ml dimethylformamide. Reaction mixture was stirred at room temperature for one hour and 5-(4-[1-imidazolyl]-phenylsulfonyloxy)-1H-benzimidazole-2-ylamine was added in 0.2 ml dimethylformamide. Reaction mixture was then stirred at room temperature for 24 hours. Solvent was evaporated in a Jouan model RC 10.10 centrifuge evaporator and title compound was solubilised in 0.5 ml dimethylsulfoxide for LCMS trigged purification yielding 3.9 mg of N-[5-(4-[1-imidazolyl]-phenylsulfonyloxy)-1H-benzimidazole-2-yl]-succinamic-acid-methyl ester. (LC/MS analysis: retention time=2.70 min., mass spectrum: 470.34, [M+H]+). Reaction mixture Reaction mixture was then stirred at room temperature for 24 hours Solvent was evaporated in a Jouan model RC 10.10 centrifuge evaporator and title compound purification

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

Procedure: Using a method similar to the procedure described for the preparation of 4-[4-(2-nitro-phenyl)-oxazol-2-yl]-butyric acid methyl ester; reaction of 2-bromo-2′-nitroacetophenone (15.43 g, 63.2 mmol) with succinamic acid methyl ester (14.4 g, 110 mmol) gives 3-[4-(2-nitro-phenyl)-oxazol-2-yl]-propionic acid methyl ester (6.24 g, 36%). MS (ES): (M+1)+ 277.1 m/z.

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

Procedure: Using a method similar to the procedure described for the preparation of 4-[4-(2-nitro-phenyl)-oxazol-2-yl]-butyric acid methyl ester; reaction of 2-bromo-2′-nitroacetophenone (15.43 g, 63.2 mmol) with succinamic acid methyl ester (14.4 g, 110 mmol) gives 3-[4-(2-nitro-phenyl)-oxazol-2-yl]-propionic acid methyl ester (6.24 g, 36%). MS (ES): (M+1)+ 277.1 m/z.

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

Procedure: A solution of methyl succinamate (2.5 g, 0.019 mol) in THF (60 mL) was cooled to 0° C. and P2S5 (4.2 g, 0.019 mol) was added. The reaction mixture was warmed to room temperature and stirred for 6 h. The solvent was removed under reduced pressure and the crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 35-40% EtOAc in petroleum ether) to afford methyl 4-amino-4-thioxobutanoate (1.6 g, yield 57%). 1H NMR (300 MHz, CDCl3) δ 7.49 (br s, 2H), 3.72 (s, 3H), 2.95-2.86 (m, 4H). MS (ESI) m/z: Calculated for C5H9NO2S: 147.04. found: 248.2 (M+H)+. The solvent was removed under reduced pressure the crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 35-40% EtOAc in petroleum ether)

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

Procedure: Methyl succinamate (2 g, 15.2 mmol) was dissolved in dry THF (50 mL) and P2S5 (3.4 g, 15.2 mmol) was added and the reaction mixture was stirred at room temperature for 6 h. The reaction mixture was filtered through a sintered funnel and the clear filtrate was concentrated under reduced pressure to get the crude product, which was further purified by column chromatography (silica gel 60-120 mesh, eluent 50% EtOAc in petroleum ether) to afford methyl 4-amino-4-thioxobutanoate (1.25 g, yield 53%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.27 (br s, 2H), 3.72 (s, 3H), 2.96-2.85 (m, 4H). MS (ESI) m/z: Calculated for C5H9NO2S: 147.04. found: 148.2 (M+H)+. The reaction mixture was filtered through a sintered funnel the clear filtrate was concentrated under reduced pressure to get the crude product, which was further purified by column chromatography (silica gel 60-120 mesh, eluent 50% EtOAc in petroleum ether)