2-(8-bromooctyl)isoindole-1,3-dione

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

Procedure: To a round bottom flask with 2-mercaptobenzoxazole (2.14 g, 14.2 mmol) andDMF (100 mL) at room temperature was added K2CO3 (2.61 g, 18.9 mmol) followed by N-(8-bromooctyl)phthalimide (4.00 g, 11.8 mmol). The resulting solution was heated to 60° C. for 0.5 h and then cooled back to room temperature. At this point, the reaction mixture was quenched with H2O (100 mL) and then diluted with EtOAc (600 mL). The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient) to afford the thioether intermediate. cooled back to room temperature At this point, the reaction mixture was quenched with H2O (100 mL) diluted with EtOAc (600 mL) The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) dried (MgSO4) After concentration the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient)

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

Procedure: To a round bottom flask with 2-mercaptobenzoxazole (2.14 g, 14.2 mmol) andDMF (100 mL) at room temperature was added K2CO3 (2.61 g, 18.9 mmol) followed by N-(8-bromooctyl)phthalimide (4.00 g, 11.8 mmol). The resulting solution was heated to 60° C. for 0.5 h and then cooled back to room temperature. At this point, the reaction mixture was quenched with H2O (100 mL) and then diluted with EtOAc (600 mL). The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient) to afford the thioether intermediate. cooled back to room temperature At this point, the reaction mixture was quenched with H2O (100 mL) diluted with EtOAc (600 mL) The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) dried (MgSO4) After concentration the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient)

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

Procedure: To a round bottom flask with 2-mercaptobenzoxazole (2.14 g, 14.2 mmol) andDMF (100 mL) at room temperature was added K2CO3 (2.61 g, 18.9 mmol) followed by N-(8-bromooctyl)phthalimide (4.00 g, 11.8 mmol). The resulting solution was heated to 60° C. for 0.5 h and then cooled back to room temperature. At this point, the reaction mixture was quenched with H2O (100 mL) and then diluted with EtOAc (600 mL). The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient) to afford the thioether intermediate. cooled back to room temperature At this point, the reaction mixture was quenched with H2O (100 mL) diluted with EtOAc (600 mL) The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) dried (MgSO4) After concentration the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient)

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

Procedure: Sodium hydride (120 mg of a 60% dispersion in mineral oil) was added to a solution of 5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine (906 mg) in dry dimethylformamide (30 ml) with stirring under nitrogen. The mixture was stirred for 30 minutes under nitrogen and then N-(8-bromooctyl)phthalimide (1.4 g) in dimethyl-formamide (5 ml) was added. The mixture was stirred at ambient temperature for 18 hours under nitrogen and then partitioned between water and ethyl acetate. The ethyl acetate layer was separated and purified by flash column chromatography using ethyl acetate as the mobile phase to give 5-(4-phenoxyphenyl)-7-(8-phthalimidooctyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine, m.p. 85-86° C. The mixture was stirred for 30 minutes under nitrogen The mixture was stirred at ambient temperature for 18 hours under nitrogen partitioned between water and ethyl acetate The ethyl acetate layer was separated purified by flash column chromatography

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

Procedure: Sodium hydride (120 mg of a 60% dispersion in mineral oil) was added to a solution of 5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine (906 mg) in dry dimethylformamide (30 ml) with stirring under nitrogen. The mixture was stirred for 30 minutes under nitrogen and then N-(8-bromooctyl)phthalimide (1.4 g) in dimethyl-formamide (5 ml) was added. The mixture was stirred at ambient temperature for 18 hours under nitrogen and then partitioned between water and ethyl acetate. The ethyl acetate layer was separated and purified by flash column chromatography using ethyl acetate as the mobile phase to give 5-(4-phenoxyphenyl)-7-(8-phthalimidooctyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine, m.p. 85-86° C. The mixture was stirred for 30 minutes under nitrogen The mixture was stirred at ambient temperature for 18 hours under nitrogen partitioned between water and ethyl acetate The ethyl acetate layer was separated purified by flash column chromatography

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

Procedure: To a round bottom flask with 2-mercaptobenzoxazole (2.14 g, 14.2 mmol) and DMF (100 mL) at room temperature was added K2CO3 (2.61 g, 18.9 mmol) followed by N-(8-bromooctyl)phthalimide (4.00 g, 11.8 mmol). The resulting solution was heated to 60° C. for 0.5 h and then cooled back to room temperature. At this point, the reaction mixture was quenched with H2O (100 m]L) and then diluted with EtOAc (600 mL). The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient) to afford the thioether intermediate. cooled back to room temperature At this point, the reaction mixture was quenched with H2O (100 m]L) and then diluted with EtOAc (600 mL) The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) dried (MgSO4) After concentration the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient)

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

Procedure: To a round bottom flask with 2-mercaptobenzoxazole (2.14 g, 14.2 mmol) and DMF (100 mL) at room temperature was added K2CO3 (2.61 g, 18.9 mmol) followed by N-(8-bromooctyl)phthalimide (4.00 g, 11.8 mmol). The resulting solution was heated to 60° C. for 0.5 h and then cooled back to room temperature. At this point, the reaction mixture was quenched with H2O (100 mL) and then diluted with EtOAc (600 mL). The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient) to afford the thioether intermediate. cooled back to room temperature At this point, the reaction mixture was quenched with H2O (100 mL) diluted with EtOAc (600 mL) The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) dried (MgSO4) After concentration the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient)

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

Procedure: To a round bottom flask with 2-mercaptobenzoxazole (2.14 g, 14.2 mmol) and DMF (100 mL) at room temperature was added K2CO3 (2.61 g, 18.9 mmol) followed by N-(8-bromooctyl)phthalimide (4.00 g, 11.8 mmol). The resulting solution was heated to 60° C. for 0.5 h and then cooled back to room temperature. At this point, the reaction mixture was quenched with H2O (100 mL) and then diluted with EtOAc (600 mL). The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient) to afford the thioether intermediate. cooled back to room temperature At this point, the reaction mixture was quenched with H2O (100 mL) diluted with EtOAc (600 mL) The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) dried (MgSO4) After concentration the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient)

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

Procedure: To a round bottom flask with 2-mercaptobenzoxazole (2.14 g, 14.2 mmol) andDMF (100 mL) at room temperature was added K2CO3 (2.61 g, 18.9 mmol) followed by N-(8-bromooctyl)phthalimide (4.00 g, 11.8 mmol). The resulting solution was heated to 60° C. for 0.5 h and then cooled back to room temperature. At this point, the reaction mixture was quenched with H2O (100 mL) and then diluted with EtOAc (600 mL). The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient) to afford the thioether intermediate. cooled back to room temperature At this point, the reaction mixture was quenched with H2O (100 mL) diluted with EtOAc (600 mL) The organic layer was washed with 1 N HCl (60 mL), sat. aq. NaHCO3 (60 mL), and brine (60 mL) dried (MgSO4) After concentration the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc/petroleum ether gradient)

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

Procedure: Sodium hydride (120 mg of a 60% dispersion in mineral oil) was added to a solution of 5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine (906 mg) in dry dimethylformamide (30 ml) with stirring under nitrogen. The mixture was stirred for 30 minutes under nitrogen and then N-(8-bromooctyl)phthalimide (1.4 g) in dimethyl-formamide (5 ml) was added. The mixture was stirred at ambient temperature for 18 hours under nitrogen and then partitioned between water and ethyl acetate. The ethyl acetate layer was separated and purified by flash column chromatography using ethyl acetate as the mobile phase to give 5-(4-phenoxyphenyl)-7-(8-phthalimidooctyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine, m.p. 85-86° C. The mixture was stirred for 30 minutes under nitrogen The mixture was stirred at ambient temperature for 18 hours under nitrogen partitioned between water and ethyl acetate The ethyl acetate layer was separated purified by flash column chromatography