621-06-7

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred slurry of 500 mg (12 mmol) of a 60% oil dispersion of sodium hydride (which had been washed with hexane) in 12 ml dry DMF under argon atmosphere was added 1.06 g (5.0 mmol) of N-phenyl-2-phenyl acetamide (IVa) in 5 mL dry DMF. Gas evolution had ceased after 30 minutes and 0.560 mL (5.0 mmol) of ethyl bromoacetate was added via syringe. The solution was stirred at 25° C. for 30 minutes, then warmed to 80° C. for 4 hours. The cooled solution was carefully poured into 200 mL H2O, washed with ether, filtered over celite and acidified to pH=2. The white precipitate was filtered, washed well with H2O and dried under high vacuum to give 1.04 g (4.0 mmol, 80% yield) of 1,3-diphenyl-2,4-pyrrolidinedione Ia, mp 285°-287° C. warmed to 80° C. for 4 hours washed with ether filtered over celite The white precipitate was filtered washed well with H2O dried under high vacuum

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred slurry of 500 mg (12 mmol) of a 60% oil dispersion of sodium hydride (which had been washed with hexane) in 12 ml dry DMF under argon atmosphere was added 1.06 g (5.0 mmol) of N-phenyl-2-phenyl acetamide (IVa) in 5 mL dry DMF. Gas evolution had ceased after 30 minutes and 0.560 mL (5.0 mmol) of ethyl bromoacetate was added via syringe. The solution was stirred at 25° C. for 30 minutes, then warmed to 80° C. for 4 hours. The cooled solution was carefully poured into 200 mL H2O, washed with ether, filtered over celite and acidified to pH=2. The white precipitate was filtered, washed well with H2O and dried under high vacuum to give 1.04 g (4.0 mmol, 80% yield) of 1,3-diphenyl-2,4-pyrrolidinedione Ia, mp 285°-287° C. warmed to 80° C. for 4 hours washed with ether filtered over celite The white precipitate was filtered washed well with H2O dried under high vacuum

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 9.3 g (0.10 Mole) of aniline (IIIa) and 8.3 g (0.10 Mole) pyridine in 100 mL CH2Cl2 at 0° C. under an argon atmosphere was added a solution of 15.5 g (0.10 Mole) phenylacetyl chloride (IIa) in 25 mL CH2Cl2 over a 30 minute period. The solution was allowed to warm to 25° C. over 1 hour and was quenched into 200 mL H2O. The aqueous layer was washed with two 100 mL portions of CH2Cl2 and the combined organic layers were washed with two 100 mL portions of 10% HCl solution. The organic extract was dried over MgSO4, filtered, concentrated, and crystallized from CH2Cl2 /hexane to give 20.07 g (95%) of colorless needles. mp. 115°-116° C. δ1H-NMR (CDCl3) ppm 7.0-7.6 (m, 11 H); 3.67 (S, 2H). was quenched into 200 mL H2O The aqueous layer was washed with two 100 mL portions of CH2Cl2 the combined organic layers were washed with two 100 mL portions of 10% HCl solution The organic extract was dried over MgSO4 filtered concentrated crystallized from CH2Cl2 /hexane

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

Procedure: After the addition of anhydride THF (20 ml) to compound 5a (1.55 g, 7.34 mmol), the temperature was adjusted to 0° C. Diethyloxalate (1.45 g, 9.50 mmol) and potassium t-butoxide (1.35 g, 11.9 mmol) were added thereto and the agitation for 3 hours was carried out. After the identification of the reaction progress with TLC, the solution was poured into the distilled water and acidified with 1N HCL aqueous solution. Three times extractions were carried out with EA and three times washings were carried out with brine. Water was removed by using Na2SO4, solvents were removed and then, the suspension was carried out by HX. was adjusted to 0° C Three times extractions Water was removed were removed

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

Procedure: A mixture of 5.84 g (37.81 mmol) phenylacetyl chloride and 50 mL benzene was stirred at 0° C. A solution of 3.52 g (2.0 equivs.) aniline and 50 mL benzene was added dropwise. After addition was complete, the mixture was allowed to warm to room temperature and stirred for 3 hrs. The mixture was poured into 100 mL water and was extracted with 3×100 mL ethyl acetate. The organic layers were combined and washed sequentially with 100 mL portions of 5% aqueous hydrochloric acid, water, saturated sodium carbonate and water. The organic layer was dried, filtered and solvent was removed from the filtrate to provide 5.24 g (24.80 mmol, 65%) phenylacetanilide as a tan solid, mp=114°-116° C. NMR (CDCl3 /TMS): 3.73 (s, 2H), 7.08 (t, 1H), 7.18 (bs, 1H), 7.25-7.43 (m, 9H). Mass spectrum After addition to warm to room temperature stirred for 3 hrs was extracted with 3×100 mL ethyl acetate washed sequentially with 100 mL portions of 5% aqueous hydrochloric acid, water, saturated sodium carbonate and water The organic layer was dried filtered solvent was removed from the filtrate

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 5.84 g (37.81 mmol) phenylacetyl chloride and 50 mL benzene was stirred at 0° C. A solution of 3.52 g (2.0 equivs.) aniline and 50 mL benzene was added dropwise. After addition was complete, the mixture was allowed to warm to room temperature and stirred for 3 hrs. The mixture was poured into 100 mL water and was extracted with 3×100 mL ethyl acetate. The organic layers were combined and washed sequentially with 100 mL portions of 5% aqueous hydrochloric acid, water, saturated sodium carbonate and water. The organic layer was dried, filtered and solvent was removed from the filtrate to provide 5.24 g (24.80 mmol, 65%) phenylacetanilide as a tan solid, mp=114°-116° C. NMR (CDCl3 /TMS): 3.73 (s, 2H), 7.08 (t, 1H), 7.18 (bs, 1H), 7.25-7.43 (m, 9H). Mass spectrum After addition to warm to room temperature stirred for 3 hrs was extracted with 3×100 mL ethyl acetate washed sequentially with 100 mL portions of 5% aqueous hydrochloric acid, water, saturated sodium carbonate and water The organic layer was dried filtered solvent was removed from the filtrate

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred slurry of 500 mg (12 mmol) of a 60% oil dispersion of sodium hydride (which had been washed with hexane) in 12 ml dry DMF under argon atmosphere was added 1.06 g (5.0 mmol) of N-phenyl-2-phenyl acetamide (IVa) in 5 mL dry DMF. Gas evolution had ceased after 30 minutes and 0.560 mL(5.0 mmol) of ethyl bromoacetate was added via syringe. The solution was stirred at 25° C. for 30 minutes, then warmed to 80° C. for 4 hours. The cooled solution was carefully poured into 200 mL H2O, washed with ether, filtered over celite and acidified to pH=2. The white precipitate was filtered, washed well with H2O and dried under high vacuum to give 1.04 g (4.0 mmol, 80% yield) of 1,3-diphenyl-2,4-pyrrolidinedione Ia, mp 285°-287° C. warmed to 80° C. for 4 hours washed with ether filtered over celite The white precipitate was filtered washed well with H2O dried under high vacuum

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 9.3 g (0.10 Mole) of aniline (IIIa) and 8.3 g (0.10 Mole) pyridine in 100 mL CH2Cl2 at 0° C. under an argon atmosphere was added a solution of 15.5 g (0.10 Mole) phenylacetyl chloride (IIa) in 25 mL CH2Cl2 over a 30 minute period. The solution was allowed to warm to 25° C. over 1 hour and was quenched into 200 mL H2O. The aqueous layer was washed with two 100 mL portions of CH2Cl2 and the combined organic layers were washed with two 100 mL portions of 10% HCl solution The organic extract was dried over MgSO4, filtered, concentrated, and crystallized from CH2Cl2 /hexane to give 20.07 g (95%) of colorless needles. mp. 115°-116° C. δ1H-NMR (CDCl3) ppm 7.0-7.6 (m,11 H); 3.67 (S,2 H). was quenched into 200 mL H2O The aqueous layer was washed with two 100 mL portions of CH2Cl2 the combined organic layers were washed with two 100 mL portions of 10% HCl solution The organic extract was dried over MgSO4 filtered concentrated crystallized from CH2Cl2 /hexane

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

Procedure: To a mixture of 2-(4-methylpiperazin-1-yl)benzaldehyde (0.157 g, 0.77 mmol), 2,N-diphenylacetamide (0.162 g, 0.77 mmol), benzene (1.0 mL) and N,N-dimethylformamide (1.1 mL) was added anhydrous sodium methoxide (0.087 g, 1.62 mmol). Under a nitrogen atmosphere (N2), the mixture was heated to 80° C. for 16 hours, at which time another 46 mg of sodium methoxide (NaOCH3) was added and heating continued at 130° C. for 7 hours. The reaction was cooled to room temperature and was diluted with ethyl acetate (EtOAc), washed twice with 1N lithium chloride (LiCl), once with saturated aqueous sodium chloride, and dried over calcium sulfate (CaSO4). After filtration, the crude product was absorbed onto 450 mg of silica gel and added to a 4.0×8 inch column packed with silica gel and ethyl acetate. Elution with ethyl acetate (200 mL) followed by 1% methanol: 99% ethyl acetate (100 mL) gave 35 mg of a light yellow oil which was crystallized from methylene chloride:hexanes to give the title product, 5 mg, as a yellow powder. was added heating washed twice with 1N lithium chloride (LiCl), once with saturated aqueous sodium chloride dried over calcium sulfate (CaSO4) After filtration the crude product was absorbed onto 450 mg of silica gel added to a 4.0×8 inch column Elution with ethyl acetate (200 mL)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred slurry of 500 mg (12 mmol) of a 60% oil dispersion of sodium hydride (which had been washed with hexane) in 12 ml dry DMF under argon atmosphere was added 1.06 g (5.0 mmol) of N-phenyl-2-phenyl acetamide (IVa) in 5 mL dry DMF. Gas evolution had ceased after 30 minutes and 0.560 mL (5.0 mmol) of ethyl bromoacetate was added via syringe. The solution was stirred at 25° C. for 30 minutes, then warmed to 80° C. for 4 hours. The cooled solution was carefully poured into 200 mL H2O, washed with ether, filtered over celite and acidified to pH=2. The white precipitate was filtered, washed well with H2O and dried under high vacuum to give 1.04 g (4.0 mmol, 80% yield) of 1,3-diphenyl-2,4-pyrrolidinedione Ia, mp 285°-287° C. warmed to 80° C. for 4 hours washed with ether filtered over celite The white precipitate was filtered washed well with H2O dried under high vacuum