3,4-dibromo-1-methylpyrrole-2,5-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:0.00; pressure:0.00; stir:

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

Procedure: A solution containing 1.445 g of indole, dissolved in 29 ml of dry tetrahydrofuran, is held between −20 and −10° C. under argon, and then 26 ml of LiHMDS (1M in hexane) are added, dropwise, over the course of 15 minutes. After 45 minutes at −10° C., the solution is diluted with 15 ml of additional tetrahydrofuran, and a solution containing 2 g of N-methyl-2,3-dibromomaleimide dissolved in 17 ml of tetrahydrofuran is added dropwise over the course of 30 minutes. After 15 minutes at −10° C. and 15 minutes at 0° C., the reaction is stopped by the addition, at 0° C., of 50 ml of 0.3N hydrochloric acid solution. The reaction mixture is extracted with ethyl acetate, and the organic phases are washed with saturated NaCl solution, dried over MgSO4 and then evaporated under reduced pressure. The desired product is precipitated using methanol. is held between −20 and −10° C. under argon over the course of 15 minutes is added dropwise over the course of 30 minutes After 15 minutes at −10° C. The reaction mixture is extracted with ethyl acetate the organic phases are washed with saturated NaCl solution dried over MgSO4 evaporated under reduced pressure The desired product is precipitated

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

Procedure: A solution containing 1.445 g of indole, dissolved in 29 ml of dry tetrahydrofuran, is held between −20 and −10° C. under argon, and then 26 ml of LiHMDS (1M in hexane) are added, dropwise, over the course of 15 minutes. After 45 minutes at −10° C., the solution is diluted with 15 ml of additional tetrahydrofuran, and a solution containing 2 g of N-methyl-2,3-dibromomaleimide dissolved in 17 ml of tetrahydrofuran is added dropwise over the course of 30 minutes. After 15 minutes at −10° C. and 15 minutes at 0° C., the reaction is stopped by the addition, at 0° C., of 50 ml of 0.3N hydrochloric acid solution. The reaction mixture is extracted with ethyl acetate, and the organic phases are washed with saturated NaCl solution, dried over MgSO4 and then evaporated under reduced pressure. The desired product is precipitated using methanol. is held between −20 and −10° C. under argon over the course of 15 minutes is added dropwise over the course of 30 minutes After 15 minutes at −10° C. The reaction mixture is extracted with ethyl acetate the organic phases are washed with saturated NaCl solution dried over MgSO4 evaporated under reduced pressure The desired product is precipitated

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

Procedure: A solution of ethylmagnesium bromide is prepared, starting from magnesium (12.7 mmol) suspended in bromoethane (12.7 mmol) and dry tetrahydrofuran (5 ml). The solution is stirred at ambient temperature for 1 hour and then 7-azaindole (12.7 mmol), dissolved in 40 ml of anhydrous toluene, is added dropwise. After stirring at ambient temperature for 1 hour 30 minutes, a solution of N-methyl-2,3-dibromomaleimide (3.53 mmol) in 40 ml of anhydrous toluene is added dropwise. After 20 minutes, 60 ml of dry dichloromethane are added; the reaction mixture is then stirred at 40° C. for 75 hours and hydrolysed with saturated aqueous ammonium chloride solution. The organic product is extracted with ethyl acetate, and the organic phases are then combined, dried over magnesium sulphate and filtered. After evaporating off the solvent and purifying the residue by chromatography on silica gel (cyclohexane/ethyl acetate: 3/2), the expected product is isolated. is added dropwise After stirring at ambient temperature for 1 hour 30 minutes After 20 minutes The organic product is extracted with ethyl acetate dried over magnesium sulphate filtered After evaporating off the solvent purifying the residue by chromatography on silica gel (cyclohexane/ethyl acetate: 3/2)

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

Procedure: A solution of 1.445 g of indole dissolved in 29 ml of dry tetrahydrofliran is brought to from −20 to −10° C. under argon, and then 26 ml of LiHMDS (1M in hexane) are added dropwise in the course of 15 minutes. After 45 minutes at −10° C., the solution is diluted with an additional 15 ml of tetrahydrofuran and a solution of 2 g of N-methyl-2,3-dibromomaleimide dissolved in 17 ml of tetrahydrofuran is added dropwise in the course of 30 minutes. After 15 minutes at −10° C. and 15 minutes at 0° C., the reaction is stopped by the addition, at 0° C., of 50 ml of a 0.3N hydrochloric acid solution. The reaction mixture is extracted with ethyl acetate, and the organic phases are washed with a saturated NaCl solution, dried over MgSO4 and then evaporated under reduced pressure. The desired product is precipitated using methanol. is brought to from −20 to −10° C. under argon is added dropwise in the course of 30 minutes After 15 minutes at −10° C. The reaction mixture is extracted with ethyl acetate the organic phases are washed with a saturated NaCl solution dried over MgSO4 evaporated under reduced pressure The desired product is precipitated

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

Procedure: To a stirred solution of 3,4-dibromo-1-methyl-1H-pyrrole-2,5-dione (100 mg, 0.373 mmol) in AcN (20 mL) was added piperidin-4-one hydrochloride (101 mg, 0.746 mmol) at room temperature followed by K2CO3 (102 mg, 7.46 mol). The reaction mixture was then refluxed for 2 h, diluted with water, extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude material was purified via silica gel column chromatography eluting with 30% EtOAc in hexanes to afford 3-bromo-1-methyl-4-(4-oxopiperidin-1-yl)-1H-pyrrole-2,5-dione (100 mg, 99%) as a pale yellow solid. The reaction mixture was then refluxed for 2 h extracted with EtOAc (2×20 mL) The combined organic layers were washed with brine dried over anhydrous Na2SO4 filtered concentrated in vacuo The crude material was purified via silica gel column chromatography eluting with 30% EtOAc in hexanes

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

Procedure: To a stirred solution of 3,4-dibromo-1-methyl-1H-pyrrole-2,5-dione (100 mg, 0.373 mmol) in AcN (20 mL) was added piperidin-4-one hydrochloride (101 mg, 0.746 mmol) at room temperature followed by K2CO3 (102 mg, 7.46 mol). The reaction mixture was then refluxed for 2 h, diluted with water, extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude material was purified via silica gel column chromatography eluting with 30% EtOAc in hexanes to afford 3-bromo-1-methyl-4-(4-oxopiperidin-1-yl)-1H-pyrrole-2,5-dione (100 mg, 99%) as a pale yellow solid. The reaction mixture was then refluxed for 2 h extracted with EtOAc (2×20 mL) The combined organic layers were washed with brine dried over anhydrous Na2SO4 filtered concentrated in vacuo The crude material was purified via silica gel column chromatography eluting with 30% EtOAc in hexanes

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

Procedure: To a room temperature, stirred solution of 2,3-dibromo-N-methylmaleimide (1 g, 0.004 mol) in DMF (10 mL) was added Cs2CO3 (1.34 g, 0.004 mol) followed by morpholine (360 mg, 0.004 mol) under N2 atmosphere. The reaction mixture was then stirred for 30 minutes, quenched with ice water, and extracted with EtOAc (2×50 mL). The combined organic layers were washed with water, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford 3-bromo-1-methyl-4-morpholino-1H-pyrrole-2,5-dione (0.87 g, 85%) as a solid. quenched with ice water extracted with EtOAc (2×50 mL) The combined organic layers were washed with water dried over anhydrous Na2SO4 filtered concentrated in vacuo