1,5-Dihydro-benzo[b][1,4]diazepine-2,4-dione

反应条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred suspension of the product from Example 8-P, Step A (1.0 eq., 17.08 g) in DMSO (500 mL) at room temperature was added neopentyl iodide (43.01 g, 2.24 eq., Aldrich) and Cs2CO3 (72.65 g, 2.3 eq., Aldrich). The resulting mixture was heated to 75° C. for 30 minutes, then additional Cs2CO3 (31.59 g, 1.0 eq.) was added and the mixture rapidly stirred at 75° C. for 6 hours. The mixture was allowed to cool and H2O (500 mL) and EtOAc (1000 mL) were added. The phases were partitioned and the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL). Then, the organic phase was dried over MgSO4, filtered, concentrated, and purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3) to provide 2,4-dioxo-1,5-bis-(2,2-dimethylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine as a white solid. to cool The phases were partitioned the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL) Then, the organic phase was dried over MgSO4 filtered concentrated purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3)

反应条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred suspension of the product from Example 8-P, Step A (1.0 eq., 17.08 g) in DMSO (500 mL) at room temperature was added neopentyl iodide (43.01 g, 2.24 eq., Aldrich) and Cs2CO3 (72.65 g, 2.3 eq., Aldrich). The resulting mixture was heated to 75° C. for 30 minutes, then additional Cs2CO3 (31.59 g, 1.0 eq.) was added and the mixture rapidly stirred at 75° C. for 6 hours. The mixture was allowed to cool and H2O (500 mL) and EtOAc (1000 mL) were added. The phases were partitioned and the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL). Then, the organic phase was dried over MgSO4, filtered, concentrated, and purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3) to provide 2,4-dioxo-1,5-bis-(2,2-dimethylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine as a white solid. to cool The phases were partitioned the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL) Then, the organic phase was dried over MgSO4 filtered concentrated purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,4-Dioxo-1,5-bis-(cyclopropylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was prepared following General Procedure 8-M using the product from Example 8-P, Step A and (bromomethyl)cyclopropane (Lancaster). Purification was by flash chromatography eluting with EtOAc/hexanes (3:7 gradient to straight EtOAc), then recrystalization from EtOAc/hexanes. Purification eluting with EtOAc/hexanes (3:7 gradient to straight EtOAc) recrystalization from EtOAc/hexanes

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,4-Dioxo-1,5-bis-(2-methylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was prepared following General Procedure 8-M using the product from Example 8-P, Step A and 1-iodo-2-methylpropane (Aldrich). Purification was by flash chromatography eluting with EtOAc/hexanes (3:7 gradient to 1:1), then recrystalization from EtOAc/hexanes. Purification eluting with EtOAc/hexanes (3:7 gradient to 1:1) recrystalization from EtOAc/hexanes

反应条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred suspension of the product from Example 8-P, Step A (1.0 eq., 17.08 g) in DMSO (500 mL) at room temperature was added neopentyl iodide (43.01 g, 2.24 eq., Aldrich) and Cs2CO3 (72.65 g, 2.3 eq., Aldrich). The resulting mixture was heated to 75° C. for 30 minutes, then additional Cs2CO3 (31.59 g, 1.0 eq.) was added and the mixture rapidly stirred at 75° C. for 6 hours. The mixture was allowed to cool and H2O (500 mL) and EtOAc (1000 mL) were added. The phases were partitioned and the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL). Then, the organic phase was dried over MgSO4, filtered, concentrated, and purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3) to provide 2,4-dioxo-1,5-bis-(2,2-dimethylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine as a white solid. to cool The phases were partitioned the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL) Then, the organic phase was dried over MgSO4 filtered concentrated purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,4-Dioxo-1,5-bis-(cyclopropylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was prepared following General Procedure 8-M using the product from Example 8-P, Step A, and (bromomethyl)cyclopropane (Lancaster). Purification was by flash chromatography eluting with EtOAc/hexanes (3:7 gradient to straight EtOAc), then recrystalization from EtOAc/hexanes. Purification eluting with EtOAc/hexanes (3:7 gradient to straight EtOAc) recrystalization from EtOAc/hexanes

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,4-Dioxo-1,5-bis-(2-methylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was prepared following General Procedure 8-M using the product from Example 8-P, Step A and 1-iodo-2-methylpropane (Aldrich). Purification was by flash chromatography eluting with EtOAc/hexanes (3:7 gradient to 1:1), then recrystalization from EtOAc/hexanes. Purification eluting with EtOAc/hexanes (3:7 gradient to 1:1) recrystalization from EtOAc/hexanes

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,4-Dioxo-1,5-bis-(2-methylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was prepared following General Procedure 8-M using the product from Example 8-P, Step A and 1-iodo-2-methylpropane (Aldrich). Purification was by flash chromatography eluting with EtOAc/hexanes (3:7 gradient to 1:1), then recrystalization from EtOAc/hexanes. Purification eluting with EtOAc/hexanes (3:7 gradient to 1:1) recrystalization from EtOAc/hexanes

反应条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred suspension of the product from Example 8-P, Step A (1.0 eq., 17.08 g) in DMSO (500 mL) at room temperature was added neopentyl iodide (43.01 g, 2.24 eq., Aldrich) and Cs2CO3 (72.65 g, 2.3 eq., Aldrich). The resulting mixture was heated to 75° C. for 30 minutes, then additional Cs2CO3 (31.59 g, 1.0 eq.) was added and the mixture rapidly stirred at 75° C. for 6 hours. The mixture was allowed to cool and H2O (500 mL) and EtOAc (1000 mL) were added. The phases were partitioned and the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL). Then, the organic phase was dried over MgSO4, filtered, concentrated, and purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3) to provide 2,4-dioxo-1,5-bis-(2,2-dimethylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine as a white solid. to cool The phases were partitioned the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL) Then, the organic phase was dried over MgSO4 filtered concentrated purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,4-Dioxo-1,5-bis-cyclopropylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was prepared following General Procedure 8-M using the product from Example 8-P, Step A, and (bromomethyl)cyclopropane (Lancaster). Purification was by flash chromatography eluting with EtOAc/hexanes (3:7 gradient to straight EtOAc), then recrystallization from EtOAc/hexanes. Purification eluting with EtOAc/hexanes (3:7 gradient to straight EtOAc) recrystallization from EtOAc/hexanes

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,4-Dioxo-1,5-bis-(2-methylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was prepared following General Procedure 8-M using the product from Example 8-P, Step A and 1-iodo-2-methylpropane (Aldrich). Purification was by flash chromatography eluting with EtOAc/hexanes (3:7 gradient to 1:1), then recrystallization from EtOAc/hexanes. Purification eluting with EtOAc/hexanes (3:7 gradient to 1:1) recrystallization from EtOAc/hexanes

反应条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred suspension of the product from Example 8-P, Step A (1.0 eq., 17.08 g) in DMSO (500 mL) at room temperature was added neopentyl iodide (43.01 g, 2.24 eq., Aldrich) and Cs2CO3 (72.65 g, 2.3 eq., Aldrich). The resulting mixture was heated to 75° C. for 30 minutes, then additional Cs2CO3 (31.59 g, 1.0 eq.) was added and the mixture rapidly stirred at 75° C. for 6 hours. The mixture was allowed to cool and H2O (500 mL) and EtOAc (1000 mL) were added. The phases were partitioned and the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL). Then, the organic phase was dried over MgSO4, filtered, concentrated, and purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3) to provide 2,4-dioxo-1,5-bis-(2,2-dimethylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine as a white solid. to cool The phases were partitioned the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL) Then, the organic phase was dried over MgSO4 filtered concentrated purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3)