2-bromo-N-methyl-N-phenylacetamide

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: 80% Sodium hydride in oil (102 mg) was added to a solution of phenylmethyl [2,3-dihydro-5-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]carbamate (1.00 g) in dry DMF (10 ml) under nitrogen. The mixture was stirred for 0.5 h at 23° and was treated with a solution of 2-bromo-N-methyl-N-phenylacetamide (707 mg) in dry DMF (1 ml). The mixture was stirred at 23° for 1 h, partitioned between phosphate buffer solution (pH6.5) and EA, the organic phase was washed with water and dried. The solvent was evaporated in vacuo and the residue was purified by chromatography on alumina. Elution with MeOH-DCM (1:50) gave the title compound (568 mg). The mixture was stirred at 23° for 1 h partitioned between phosphate buffer solution (pH6.5) and EA the organic phase was washed with water dried The solvent was evaporated in vacuo the residue was purified by chromatography on alumina Elution with MeOH-DCM (1:50)

Conditions: temp:67.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Nitrophenol S7 (2.8 g), anhydrous potassium carbonate (4.1 g), and N-methyl-N-phenyl-2-bromoacetamide (4.5 g) were suspended in N,N-dimethylformamide (50 ml), and the resulting suspension was stirred at 65-70° C. for 3 hours. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with water and brine, then dried over anhydrous magnesium sulfate. The solvent was distilled off, obtaining 5.4 g of the compound S8. extracted with ethyl acetate The extract was washed with water and brine dried over anhydrous magnesium sulfate The solvent was distilled off

Conditions: temp:67.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Nitrophenol S7 (2.8 g), anhydrous potassium carbonate (4.1 g), and N-methyl-N-phenyl-2-bromoacetamide (4.5 g) were suspended in N,N-dimethylformamide (50 ml), and the resulting suspension was stirred at 65-70° C. for 3 hours. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with water and brine, then dried over anhydrous magnesium sulfate. The solvent was distilled off, obtaining 5.4 g of the compound S8. extracted with ethyl acetate The extract was washed with water and brine dried over anhydrous magnesium sulfate The solvent was distilled off

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

Procedure: To 0.50 g (2.2 mmole) of 3-pentafluoroethyl-5-hydroxyisoxazole sodium salt were added dry acetonitrile (7 ml) and N-methyl-N-phenyl-2-bromoacetamide (0.55 g) and the resulting mixture was stirred at 60° C. for 24 hours. After completion of reaction, the reaction solution was evaporated under reduced pressure and to the residue was added water (80 ml), extracted with methylene chloride, treated with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel to give 0.52 g of crystals. These crystals were recrystallized from n-hexane to give 0.48 g of the titled compound as colorless plates, yield 62.3%, m.p. 88.0-89.0° C. After completion of reaction the reaction solution was evaporated under reduced pressure and to the residue was added water (80 ml) extracted with methylene chloride treated with anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by chromatography on silica gel

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 mixture of 2-bromo-N-methyl-N-phenyl-acetamide ((Example 39a) (38 mg) and 1-phenyl-cycloheptanecarboxylic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester (Example 14e) (50 mg) in 1 mL MeCN was stirred at room temperature for 48 h. The volatiles were evaporated and the residue purified by silica gel chromatography eluting with 0-10% MeOH/dichloromethane. Further purification by reverse phase HPLC eluting with 20-90% MeCN/H2O containing 0.1% formic acid gave the title compound (17 mg) as a colourless gum. The volatiles were evaporated the residue purified by silica gel chromatography eluting with 0-10% MeOH/dichloromethane Further purification by reverse phase HPLC eluting with 20-90% MeCN/H2O containing 0.1% formic acid

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

Procedure: To a mixture of N-methyl aniline (5 mL) and potassium carbonate (9.6 g) in 100 mL dichloromethane was added bromoacetyl bromide (8.1 mL) (exotherm). The mixture was stirred for 4.5h then water was added. The phases were separated and the organic layer was concentrated. The crude product was purified by silica gel chromatography eluting with 0-100% EtOAc/cyclohexane. The relevant fractions were combined and evaporated and the residue was taken up in dichloromethane and washed with water. The organic layer was stirred with another portion of water for a few minutes and then the layers were separated. Evaporation of the organic layer gave the sub-titled compound (10.2 g) as a straw coloured solid. The phases were separated the organic layer was concentrated The crude product was purified by silica gel chromatography eluting with 0-100% EtOAc/cyclohexane evaporated washed with water the layers were separated Evaporation of the organic layer

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

Procedure: 80% Sodium hydride in oil (102 mg) was added to a solution of phenylmethyl [2,3-dihydro-5-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]carbamate (1.00 g) in dry DMF (10 ml) under nitrogen. The mixture was stirred for 0.5 h at 23° and was treated with a solution of 2-bromo-N-methyl-N-phenylacetamide (707 mg) in dry DMF (1 ml). The mixture was stirred at 23° for 1 h, partitioned between phosphate buffer solution (pH6.5) and EA, the organic phase was washed with water and dried. The solvent was evaporated in vacuo and the residue was purified by chromatography on alumina. Elution with MeOH-DCM (1:50) gave the title compound (568 mg). The mixture was stirred at 23° for 1 h partitioned between phosphate buffer solution (pH6.5) and EA the organic phase was washed with water dried The solvent was evaporated in vacuo the residue was purified by chromatography on alumina Elution with MeOH-DCM (1:50)