2-bromo-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: To a stirred solution of aniline (7.40 mmol) in methylene chloride (25 mL) at −50° C. was added successively N,N-diisopropylethylamine (1.58 mL, 8.14 mmol, 1.1 eq) and bromoacetyl bromide (0.72 mL, 7.40 mmol, 1 eq) such that the temperature did not exceed 40° C. On completion of the addition, the cooling bath was removed, and the reaction mixture was allowed to warm to room temperature. After stirring for a further 30 minutes, the mixture was diluted with ether (70 mL) and poured into 1 N sodium bisulfate solution. The phases were separated, and the upper layer was washed successively with water and brine. The organic phase was dried (Na2SO4) and the solvent evaporated to half volume, at which point the product crystallized. The crystals were removed by vacuum filtration to afford the title compound. did not exceed 40° C On completion of the addition the cooling bath was removed the mixture was diluted with ether (70 mL) poured into 1 N sodium bisulfate solution The phases were separated the upper layer was washed successively with water and brine The organic phase was dried (Na2SO4) the solvent evaporated to half volume, at which point the product crystallized The crystals were removed by vacuum filtration

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

Procedure: To a magnetically stirred mixture of ethyl 5-methyl-1H-pyrazole-3-carboxylate (0.02 mol) and sodium ethoxide (0.22 mol) in ethanol (20 mL) is added the title A compound, 2-bromo-N-phenyl-acetamide (0.02 mol). The resulting suspension is stirred at RT for 3 h. After concentration in vacuo, EtOAc is added and the resulting solution is washed twice with water and dried over anhydrous Na2SO4. After filtration and concentration, the residue is purified by flash chromatography (ethyl acetate/hexane) to afford 5-methyl-1-phenylcarbamoyl-methyl-1H-pyrazole-3-carboxylic acid ethyl ester: m.p. 139-140° C.; 1H-NMR (DMSO-d6) δ 1.26-1.29 (t, 3H J=72 Hz), 2.28 (s, 3H), 4.23-4.25 (q, 2H J=72 Hz), δ 06 (s, 2H), δ 6.56 (s, 1H), 7.07 (m, 1H), 7.32 (m, 2H), 7.57 (m, 2H), 10.41 (s, 1H). After concentration in vacuo, EtOAc is added the resulting solution is washed twice with water dried over anhydrous Na2SO4 After filtration and concentration the residue is purified by flash chromatography (ethyl acetate/hexane)

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

Procedure: A solution of aniline (0.016 mol) in 40 mL of dichloromethane is cooled on ice, and 1.0 equivalent of bromoacetyl bromide in 3 mL of dichloromethane is added dropwise, followed by 0.019 mol of triethylamine (TEA). The solution turns dark and a precipate forms, as the reaction mixture is warmed to RT over 3 h. The mixture is concentrated and taken up in ethyl acetate (EtOAc) and washed three times with water. The organic phase is dried over anhydrous sodium sulphate (Na2SO4), filtered and concentrated. The residue is purified by crystallization from EtOAc to afford 2-bromo-N-phenylacetamide: m.p. 131-135° C.; 1H-NMR (CDCl3) δ 4.01 (s, 2H), 7.18 (m, 1H), 7.36 (m, 2H), 7.54 (2H), 8.09 (s, 1H). is added dropwise The mixture is concentrated washed three times with water The organic phase is dried over anhydrous sodium sulphate (Na2SO4) filtered concentrated The residue is purified by crystallization from EtOAc

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

Procedure: To a stirred solution of aniline (7.40 mmol) in methylene chloride (25 mL) at −50° C. was added successively N,N-diisopropylethylamine (1.58 mL, 8.14 mmol, 1.1 eq) and bromoacetyl bromide (0.72 mL, 7.40 mmol, 1 eq) such that the temperature did not exceed −40° C. On completion of the addition, the cooling bath was removed, and the reaction mixture was allowed to warm to room temperature. After stirring for a further 30 minutes, the mixture was diluted with ether (70 mL) and poured into 1 N sodium bisulfate solution. The phases were separated, and the upper layer was washed successively with water and brine. The organic phase was dried (Na2SO4) and the solvent evaporated to half volume, at which point the product crystallized. The crystals were removed by vacuum filtration to afford the title compound. did not exceed −40° C On completion of the addition the cooling bath was removed the mixture was diluted with ether (70 mL) poured into 1 N sodium bisulfate solution The phases were separated the upper layer was washed successively with water and brine The organic phase was dried (Na2SO4) the solvent evaporated to half volume, at which point the product crystallized The crystals were removed by vacuum filtration

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

Procedure: To a stirred solution of aniline (7.40 mmol) in methylene chloride (25 mL) at −50° C. was added successively N,N-diisopropylethylamine (1.58 mL, 8.14 mmol, 1.1 eq) and bromoacetyl bromide (0.72 mL, 7.40 mmol, 1 eq) such that the temperature did not exceed −40° C. On completion of the addition, the cooling bath was removed, and the reaction mixture was allowed to warm to room temperature. After stirring for a further 30 minutes, the mixture was diluted with ether (70 mL) and poured into 1 N sodium bisulfate solution. The phases were separated, and the upper layer was washed successively with water and brine. The organic phase was dried (Na2SO4) and the solvent evaporated to half volume, at which point the product crystallized. The crystals were removed by vacuum filtration to afford the title compound. did not exceed −40° C On completion of the addition the cooling bath was removed the mixture was diluted with ether (70 mL) poured into 1 N sodium bisulfate solution The phases were separated the upper layer was washed successively with water and brine The organic phase was dried (Na2SO4) the solvent evaporated to half volume, at which point the product crystallized The crystals were removed by vacuum filtration

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

Procedure: In 15 ml of DMF were dissolved 2.8 g of N-t-butoxycarbonyl-(S)-proline and 2.8 g of phenylcarbamoyl methyl bromide. To the solution was added 1.1 g of sodium hydrogencarbonate. The mixture was stirred at room temperature for 20 hours. The reaction mixture was poured into ice water, followed by extraction with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (using chloroform as an eluent), giving the title compound as a colorless oil. Yield 3.5 g. followed by extraction with ethyl acetate The extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and with water dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the residue was purified by silica gel column chromatography (

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

Procedure: To a suspension of ethyl 3-{(1-(3-aminophenyl)-5-oxopyrrolidin-3-yl)carbonylamino}-3-(3-pyridyl)propanoate (100 mg, 0.25 mmol, 1.1 eq), NaHCO3 (20 mg, 0.23 mmol, 1.0 eq), and CH2Cl2 (4 mL), was added 2-bromo-N-phenyl acetamide (50 mg, 0.23 mmol, 1.0 eq) in 2 mL CH2Cl2 dropwise. The reaction mixture was heated up to reflux for 5 hours, then cooled to room temperature. The reaction mixture was heated up to reflux for 5 hours

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

Procedure: The compound (7) synthesized in Reference Example 7 and the compound (23) synthesized in Reference Example 23 were used to produce the above compound in the same way as Example 1. to produce the above compound in the same way as Example 1

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

Procedure: The compound (4) synthesized in Reference Example 4 and the compound (23) synthesized in Reference Example 23 were used to produce the above compound in the same way as Example 1. to produce the above compound in the same way as Example 1