2-(2-bromophenyl)acetyl chloride

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 5-amino-4′-methyl-biphenyl-3-carboxylic acid methyl ester (241 mg, 1.0 mmol), pyridine (0.5 mL), DMAP (10 mg) and 2-bromophenylacetyl chloride (253 mg, 1.1 equiv.) was stirred for one hour at room temperature. The mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate, and the organic layer was separated and concentrated under reduced pressure to give crude 5-[2-(2-bromo-phenyl)-acetylamino]-4′-methyl-biphenyl-3-carboxylic acid methyl ester, which was used directly in the next step. The mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate the organic layer was separated concentrated under reduced pressure

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: The title compound, MS m/e (%): 484,486 (M+H+, 100), was prepared in accordance with the general method of example 31 from 2-phenyl-7-pyridin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine and o-bromphenylacetyl chloride.

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

Procedure: The title compound, MS m/e (%): 484,486 (M+H+, 100), was prepared in accordance with the general method of example 31 from 2-phenyl-7-pyridin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine and o-bromphenylacetyl chloride.

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

Procedure: Initially, 8-Bromo-2-tetralone was prepared by substituting 2-bromophenylacetylchloride in the procedure described in A. H. Horn, C. J. Grol, D. Dijkstra, A. H. Mulder, J. Med. Chem. 21, 825 (1978). Next, 8-bromo-2-tetralone (25 g, 111.1 mmol), S-(-)-alpha-methylbenzylamine (71.5 ml, 5 eq.), acetic acid (80 ml), 4 A molecular sieves (15 ml), THF (125 ml) and methanol (125 ml) were introduced into a flask and cooled to 0°. Sodium cyanoborohydride (15.1 g, 2 eq.) was added in portions over a 15 min period. The slurry was allowed to stir for 3 hr. The slurry was filtered and the solvent reduced to a syrup by evaporation in vacuo. The residue was partitioned between ether and 2N aqueous sodium hydroxide. The ether layer was washed with water (3×) and brine. After drying over anhydrous sodium sulfate the solvent was removed in vacuo. The viscous oil was placed on a flash silica gel column (5 cm×50 cm) and eluted with ethyl acetate/hexane (8%) to separate the higher Rf (+)-diastereomer (solidifies upon standing, 17g). The solvent was raised to 12% to elute the lower Rf (-)-diastereomer (an oil, 16g). In this manner the 8-bromo-N-[(S)-alpha-methylbenzyl]-2-aminotetralin was obtained. cooled to 0° The slurry was filtered the solvent reduced to a syrup by evaporation in vacuo The residue was partitioned between ether and 2N aqueous sodium hydroxide The ether layer was washed with water (3×) and brine After drying over anhydrous sodium sulfate the solvent was removed in vacuo eluted with ethyl acetate/hexane (8%) to separate the higher Rf (+)-diastereomer (solidifies upon standing, 17g) The solvent was raised to 12% to elute the lower Rf (-)-diastereomer (an oil, 16g)

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

Procedure: Initially, 8-Bromo-2-tetralone was prepared by substituting 2-bromophenylacetylchloride in the procedure described in A. H. Horn, C. J. Grol, D. Dijkstra, A. H. Mulder, J. Med. Chem. 21, 825 (1978). Next, 8-bromo-2-tetralone (25 g, 111.1 mmol), S-(-)-alpha-methylbenzylamine (71.5 ml, 5 eq.), acetic acid (80 ml), 4 A molecular sieves (15 ml), THF (125 ml) and methanol (125 ml) were introduced into a flask and cooled to 0°. Sodium cyanoborohydride (15.1 g, 2 eq.) was added in portions over a 15 min period. The slurry was allowed to stir for 3 hr. The slurry was filtered and the solvent reduced to a syrup by evaporation in vacuo. The residue was partitioned between ether and 2N aqueous sodium hydroxide. The ether layer was washed with water (3×) and brine. After drying over anhydrous sodium sulfate the solvent was removed in vacuo. The viscous oil was placed on a flash silica gel column (5 cm×50 cm) and eluted with ethyl acetate/hexane (8%) to separate the higher Rf (+)-diastereomer (solidifies upon standing, 17g). The solvent was raised to 12% to elute the lower Rf (-)-diastereomer (an oil, 16g). In this manner the 8-bromo-N-[(S)-alpha-methylbenzyl]-2-aminotetralin was obtained. cooled to 0° The slurry was filtered the solvent reduced to a syrup by evaporation in vacuo The residue was partitioned between ether and 2N aqueous sodium hydroxide The ether layer was washed with water (3×) and brine After drying over anhydrous sodium sulfate the solvent was removed in vacuo eluted with ethyl acetate/hexane (8%) to separate the higher Rf (+)-diastereomer (solidifies upon standing, 17g) The solvent was raised to 12% to elute the lower Rf (-)-diastereomer (an oil, 16g)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.72 g of 2',5'-dideoxy-5-ethyl-5'-methylaminouridine in 25 ml of dry pyridine was stirred at 0° C. and treated with a solution of (2-bromophenyl)acetyl chloride (prepared from 0.65 g of the acid by treatment with thionyl chloride in benzene under reflux) in 7 ml of benzene. The mixture was stirred at 0° C. for 0.5 hour and then stored at 4° C. overnight. The solvents were removed by evaporation and the residue was re-evaporated with toluene to give a gum which was subsequently triturated with diethyl ether to yield a solid. This solid was taken up in 5 ml of methylene chloride/methanol (9:1) and chromatographed on a column of silica gel using methylene chloride/methanol (9:1) for the elution. The fractions containing the product were combined and evaporated. The residue was re-evaporated with ethanol and recrystallized from methanol to give 0.18 g of 5'-[2-(2-bromophenyl)-N-methylacetamido]-2',5'-dideoxy-5-ethyluridine of melting point 182° -185° C. stored at 4° C. overnight The solvents were removed by evaporation the residue was re-evaporated with toluene to give a gum which was subsequently triturated with diethyl ether to yield a solid chromatographed on a column of silica gel for the elution The fractions containing the product evaporated The residue was re-evaporated with ethanol recrystallized from methanol

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

Procedure: A solution of 210 mg of (2-bromophenyl)acetyl chloride in 3 ml of diethyl ether was added to a solution of 324 mg of 5'-amino-4-N-benzoyl-2',5'-dideoxy-5-ethylcytidine in 4.9 ml of 0.18M sodium hydroxide solution and the mixture was shaken vigorously for 10 minutes. The solid was collected by filtration, washed with 2 ml of water and 1 ml of diethyl ether and recrystallized from 15 ml of ethanol to give 100 mg of 4-N-benzoyl-5'-[2-(2-bromophenyl)acetamido]-2',5'-dideoxy-5-ethylcytidine in the form of a white solid which was processed further without purification. The solid was collected by filtration washed with 2 ml of water and 1 ml of diethyl ether recrystallized from 15 ml of ethanol

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

Procedure: 0.84 ml of a 1M sodium hydroxide solution was added to a solution of 256 mg of 5'-amino-5-bromo-2',5'-dideoxycytidine in 3.3 ml of water. A solution of (2-bromophenyl)acetyl chloride (prepared from 185 mg of the acid) in 5 ml of dichloromethane was added, the mixture was shaken vigorously for 10 minutes and then filtered. The solid was recrystallized from 30 ml of ethanol to give 44 mg of 5-bromo-5'-[2-(2-bromophenyl)acetamido]-2',5'-dideoxycytidine in the form of a white solid of melting point 164°-167° C. was added filtered The solid was recrystallized from 30 ml of ethanol

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.72 g of 2',5'-dideoxy-5-ethyl-5'-methylaminouridine in 25 ml of dry pyridine was stirred at 0° C. and treated with a solution of (2-bromophenyl)acetyl chloride (prepared from 0.65 g of the acid by treatment with thionyl chloride in benzene under reflux) in 7 ml of benzene. The mixture was stirred at 0° C. for 0.5 hour and then stored at 4° C. overnight. The solvents were removed by evaporation and the residue was re-evaporated with toluene to give a gum which was subsequently triturated with diethyl ether to yield a solid. This solid was taken up in 5 ml of methylene chloride/methanol (9:1) and chromatographed on a column of silica gel using methylene chloride/methanol (9:1) for the elution. The fractions containing the product were combined and evaporated. The residue was re-evaporated with ethanol and recrystallized from methanol to give 0.18 g of 5'-[2-(2-bromophenyl)-N-methylacetamido]-2',5'-dideoxy-5-ethyluridine of melting point 182°- 185° C. stored at 4° C. overnight The solvents were removed by evaporation the residue was re-evaporated with toluene to give a gum which was subsequently triturated with diethyl ether to yield a solid chromatographed on a column of silica gel for the elution The fractions containing the product evaporated The residue was re-evaporated with ethanol recrystallized from methanol