2-but-3-enylisoindole-1,3-dione

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:

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinoline (1.9 g, 4.68 mmol), 2-but-3-enyl-1H-isoindole-1,3(2H)-dione (1.04 g, 5.15 mmol), cesium carbonate (3.05 g, 9.36 mmol), triphenylphosphine (0.246 g, 0.94 mmol), palladium(II) acetate (0.105 g, 0.47 mmol), and N,N-dimethylformamide (DMF) (28 mL) were added to a pressure tube. The vessel was sealed with a TEFLON cap and heated at 140° C. for 2.5 hours. The reaction was cooled to ambient temperature. The reaction was diluted with ethyl acetate and washed multiple times with water. The initial water wash was extracted with ethyl acetate. The organic fractions were combined and washed with water once again. The organic fractions were concentrated under reduced pressure and the residue was purified using a HORIZON HPFC system (silica cartridge, eluting with a linear gradient of 2-20% CMA in chloroform) to yield 1.9 g of 2-{(3E)-4-[2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-7-yl]but-3-enyl}-1H-isoindole-1,3(2H)-dione as a pale yellow oil. cap The reaction was cooled to ambient temperature washed multiple times with water The initial water wash was extracted with ethyl acetate washed with water once again The organic fractions were concentrated under reduced pressure the residue was purified eluting with a linear gradient of 2-20% CMA in chloroform)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinoline (1.9 g, 4.68 mmol), 2-but-3-enyl-1H-isoindole-1,3(2H)-dione (1.04 g, 5.15 mmol), cesium carbonate (3.05 g, 9.36 mmol), triphenylphosphine (0.246 g, 0.94 mmol), palladium(II) acetate (0.105 g, 0.47 mmol), and N,N-dimethylformamide (DMF) (28 mL) were added to a pressure tube. The vessel was sealed with a TEFLON cap and heated at 140° C. for 2.5 hours. The reaction was cooled to ambient temperature. The reaction was diluted with ethyl acetate and washed multiple times with water. The initial water wash was extracted with ethyl acetate. The organic fractions were combined and washed with water once again. The organic fractions were concentrated under reduced pressure and the residue was purified using a HORIZON HPFC system (silica cartridge, eluting with a linear gradient of 2-20% CMA in chloroform) to yield 1.9 g of 2-{(3E)-4-[2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-7-yl]but-3-enyl}-1H-isoindole-1,3(2H)-dione as a pale yellow oil. cap The reaction was cooled to ambient temperature washed multiple times with water The initial water wash was extracted with ethyl acetate washed with water once again The organic fractions were concentrated under reduced pressure the residue was purified eluting with a linear gradient of 2-20% CMA in chloroform)

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

Procedure: 70 g (350 mmol) 2-(but-3-enyl)-isoindolin-1,3-dione are dissolved in dichloromethane. The solution is cooled to ca. 0° C. and a suspension of 120.8 g (350 mmol) 50% 3-chloro-peroxy-benzoic acid in dichloromethane is added under cooling. The mixture is left standing without further cooling at room temperature for two days. After addition of 250 ml saturated NaHCO3 solution the organic phase is separated and washed three times each with 200 ml saturated NaHCO3 solution and once with water. The organic phase is dried over sodium sulfate and the solvent is removed under vacuum: yield 80 g. is added under cooling The mixture is left without further cooling at room temperature for two days is separated washed three times each with 200 ml saturated NaHCO3 solution The organic phase is dried over sodium sulfate the solvent is removed under vacuum

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

Procedure: 50 g (370 mmol) 4-bromo-1-butene and 68.5 g (370 mmol) phthalimide potassium salt are suspended in 800 ml ethyl methyl ketone and heated under reflux for 14 hours. After cooling, the mixture is filtrated and the filtrate is concentrated under vacuum. The residue is taken up in acetic acid ethyl ester and washed with water. The organic phase is dried over sodium sulfate and the solvent is removed under vacuum: yield 50 g (67%). heated under reflux for 14 hours After cooling the mixture is filtrated the filtrate is concentrated under vacuum washed with water The organic phase is dried over sodium sulfate the solvent is removed under vacuum

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

Procedure: To a stirred solution of 3-3 (9.1 g, 45.4 mmol) in degassed THF (50 mL) at 0° C. was added dropwise a solution of 9-BBN (110 mL of 0.5M in THF, 55 mmol) and the mixture stirred for 18 hours at ambient temperature. K2CO3 (10.8 g, 77.4 mmol) and 3-2 (5.0 g, 17.4 mmol) were added, followed by a premixed and aged (70° C. for 30 min) suspension of Pd(OAc)2 (1.2 g, 5.2 mmol) and DPPF (3.2 g, 5.6 mmol) in degassed DMF (50 mL). The resulting mixture was stirred for 18 hours at 70° C., cooled, diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated. The residue was chromatographed on silica gel (40-50% EtOAc/hexane) to give 6.2 g of 3-4 as a white solid. a premixed The resulting mixture was stirred for 18 hours at 70° C. cooled washed with water and brine dried over MgSO4 concentrated The residue was chromatographed on silica gel (40-50% EtOAc/hexane)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 4-bromo-1-butene (20 g, 148 mmol) in DMF (150 mL) was added potassium phthalimide (25 g, 133 mmol) and the mixture stirred for 18 hours at 70° C. After cooling to RT, the mixture was diluted with ether, washed with water and brine, dried over MgSO4, and concentrated to give 22.1 g of 3-3 as a white solid. After cooling to RT washed with water and brine dried over MgSO4 concentrated

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

Procedure: To a stirred solution of 8-5 (4.23 g, 21 mmol) in degassed THF (20 mL) at 0° C. was added dropwise a solution of 9-BBN (50.4 mL of 0.5 M in THF, 25.2 mmol) and the mixture stirred for 18 hours at ambient temperature. K2CO3 (5.0 g, 35.8 mmol) and 8-2 (5.0 g, 17.4 mmol) were added, followed by a premixed and aged (70° C. for 30 min) suspension of Pd(OAc)2 (0.54 g, 2.4 mmol) and DPPF (1.45 g, 2.6 mmol) in degassed DMF (20 mL). The resulting mixture was stirred for 18 hours at 70° C., cooled, diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated. To the stirring residue dissolved in THF (200 mL) was added water (75 mL) and NaHCO3 (16.5 g) and after 10 minutes, NaBO3.H2O (24 g). After vigorous stirring for 30 minutes, the mixture was diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated to an oil. The residue was chromatographed on silica gel (20–40% EtOAc/hexane) to give 8-6 as a yellow solid. a premixed The resulting mixture was stirred for 18 hours at 70° C. cooled washed with water and brine dried over MgSO4 concentrated To the stirring residue dissolved in THF (200 mL) was added water (75 mL) and NaHCO3 (16.5 g) after 10 minutes After vigorous stirring for 30 minutes the mixture was diluted with ethyl acetate washed with water and brine dried over MgSO4 concentrated to an oil The residue was chromatographed on silica gel (20–40% EtOAc/hexane)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 4-bromo-1-butene (8-3, 20 g, 148 mmol) in DMF (150 mL) was added potassium phthalimide (8-4, 25 g, 133 mmol) and the mixture stirred for 18 hours at 70° C. After cooling to RT, the mixture was diluted with ether, washed with water and brine, dried over MgSO4, and concentrated to give 8-5 as a white solid. After cooling to RT washed with water and brine dried over MgSO4 concentrated