3-methylidene-1-phenylpyrrolidine-2,5-dione

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-methylene-1-phenylazolidine-2,5-dione (250 mg, 1.33 mmol) and 1-(2-methylbenzothiazol-5-yloxy)-3-piperazin-1-ylpropan-2-ol (415 mg, 1.35 mmol) in AcOH (10 mL, glacial) was stirred 14 hours at 50° C. Concentrated in the Savant™ and residue taken up in EtOAc and washed with NaHCO3 (sat. aq. soln.), H2O and brine, dried over MgSO4, filtered and concentrated. Purification via flash column chromatography (gradient 5 to 10% MeOH/EtOAc) afforded 3-({4-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}methyl)-1-phenylazolidine-2,5-dione. Concentrated in the Savant™ and residue washed with NaHCO3 (sat. aq. soln.), H2O and brine dried over MgSO4 filtered concentrated Purification via flash column chromatography (gradient 5 to 10% MeOH/EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-methylene-1-phenylazolidine-2,5-dione (250 mg, 1.33 mmol) and 1-(2-methylbenzothiazol-5-yloxy)-3-piperazin-1-ylpropan-2-ol (415 mg, 1.35 mmol) in AcOH (10 mL, glacial) was stirred 14 hours at 50° C. Concentrated in the Savant™ and residue taken up in EtOAc and washed with NaHCO3 (sat. aq. soln.), H2O and brine, dried over MgSO4, filtered and concentrated. Purification via flash column chromatography (gradient 5 to 10% MeOH/EtOAc) afforded 3-({4-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}methyl)-1-phenylazolidine-2,5-dione. Concentrated in the Savant™ and residue washed with NaHCO3 (sat. aq. soln.), H2O and brine dried over MgSO4 filtered concentrated Purification via flash column chromatography (gradient 5 to 10% MeOH/EtOAc)

反応条件: temp:89.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of the 2-[(N-phenylcarbamoyl)methyl]prop-2-enoic acid (700 mg, 3.41 mmol) in Ac2O (15 mL) was then treated with NaOAc (327 mg, 3.98 mmol) and shaken for 14 hours at 89° C. The resulting clear solution was dried on a Savant™, dissolved in EtOAc and washed with H2O and brine. The organic layers were then dried down on Savant™ to yield 3-methylene-1-phenylazolidine-2,5-dione, a compound of formula (7′). The resulting clear solution was dried on a Savant™ dissolved in EtOAc washed with H2O and brine The organic layers were then dried down on Savant™

反応条件: temp:89.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of the 2-[(N-phenylcarbamoyl)methyl]prop-2-enoic acid (700 mg, 3.41 mmol) in Ac2O (15 mL) was then treated with NaOAc (327 mg, 3.98 mmol) and shaken for 14 hours at 89° C. The resulting clear solution was dried on a Savant™, dissolved in EtOAc and washed with H2O and brine. The organic layers were then dried down on Savant™ to yield 3-methylene-1-phenylazolidine-2,5-dione, a compound of formula (7′). The resulting clear solution was dried on a Savant™ dissolved in EtOAc washed with H2O and brine The organic layers were then dried down on Savant™

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-methylene-1-phenylazolidine-2,5-dione (250 mg, 1.33 mmol) and 1-(2-methylbenzothiazol-5-yloxy)-3-piperazin-1-ylpropan-2-ol (415 mg, 1.35 mmol) in AcOH (10 mL, glacial) was stirred 14 hours at 50° C. Concentrated in the Savant™ and residue taken up in EtOAc and washed with NaHCO3 (sat. aq. soln.), H2O and brine, dried over MgSO4, filtered and concentrated. Purification via flash column chromatography (gradient 5 to 10% MeOH/EtOAc) afforded 3-({4-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}methyl)-1-phenylazolidine-2,5-dione. Concentrated in the Savant™ and residue washed with NaHCO3 (sat. aq. soln.), H2O and brine dried over MgSO4 filtered concentrated Purification via flash column chromatography (gradient 5 to 10% MeOH/EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-methylene-1-phenylazolidine-2,5-dione (250 mg, 1.33 mmol) and 1-(2-methylbenzothiazol-5-yloxy)-3-piperazin-1-ylpropan-2-ol (415 mg, 1.35 mmol) in AcOH (10 mL, glacial) was stirred 14 hours at 50° C. Concentrated in the Savant™ and residue taken up in EtOAc and washed with NaHCO3 (sat. aq. soln.), H2O and brine, dried over MgSO4, filtered and concentrated. Purification via flash column chromatography (gradient 5 to 10% MeOH/EtOAc) afforded 3-({4-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}methyl)-1-phenylazolidine-2,5-dione. Concentrated in the Savant™ and residue washed with NaHCO3 (sat. aq. soln.), H2O and brine dried over MgSO4 filtered concentrated Purification via flash column chromatography (gradient 5 to 10% MeOH/EtOAc)

反応条件: temp:89.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of the 2-[(N-phenylcarbamoyl)methyl]prop-2-enoic acid (700 mg, 3.41 mmol) in Ac2O (15 mL) was then treated with NaOAc (327 mg, 3.98 mmol) and shaken for 14 hours at 89° C. The resulting clear solution was dried on a Savant™, dissolved in EtOAc and washed with H2O and brine. The organic layers were then dried down on Savant™ to yield 3-methylene-1-phenylazolidine-2,5-dione, a compound of formula (7′). The resulting clear solution was dried on a Savant™ dissolved in EtOAc washed with H2O and brine The organic layers were then dried down on Savant™

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-methylene-1-phenylazolidine-2,5-dione (250 mg, 1.33 mmol) and 1-(2-methylbenzothiazol-5-yloxy)-3-piperazin-1-ylpropan-2-ol (415 mg, 1.35 mmol) in AcOH (10 mL, glacial) was stirred 14 hours at 50° C. Concentrated in the Savant™ and residue taken up in EtOAc and washed with NaHCO3 (sat. aq. soln.), H2O and brine, dried over MgSO4, filtered and concentrated. Purification via flash column chromatography (gradient 5 to 10% MeOH/EtOAc) afforded 3-({4-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}methyl)-1-phenylazolidine-2,5-dione. Concentrated in the Savant™ and residue washed with NaHCO3 (sat. aq. soln.), H2O and brine dried over MgSO4 filtered concentrated Purification via flash column chromatography (gradient 5 to 10% MeOH/EtOAc)

反応条件: temp:89.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of the 2-[(N-phenylcarbamoyl)methyl]prop-2-enoic acid (700 mg, 3.41 mmol) in Ac2O (15 mL) was then treated with NaOAc (327 mg, 3.98 mmol) and shaken for 14 hours at 89° C. The resulting clear solution was dried on a Savant™, dissolved in EtOAc and washed with H2O and brine. The organic layers were then dried down on Savant™ to yield 3-methylene-1-phenylazolidine-2,5-dione, a compound of formula (7′). The resulting clear solution was dried on a Savant™ dissolved in EtOAc washed with H2O and brine The organic layers were then dried down on Savant™