4-propan-2-ylpiperazin-2-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of piperazin-2-one (1, 0.5 g, 5 mmol) and acetone (0.58 g, 10 mmol) in 1,2-dichloroethane (20 mL) was added sodium triacetoxyborohydride (3.18 g, 15.0 mmol) and the mixture was heated at 70° C. for 2 h. The mixture was diluted with EtOAc/saturated Na2CO3 (100/50 mL), washed with brine (20 mL), dried (Na2SO4), filtered and concentrated to afford the crude title compound (0.56 g, 79%). washed with brine (20 mL) dried (Na2SO4) filtered concentrated

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: To a solution 4-isopropylpiperazin-2-one (56 mg, 0.35 mmol) in DMF (3 mL) at 0° C. was added sodium hydride (18 mg, 0.45 mmol, 60% dispersion in mineral oil) and the resulting mixture stirred for 30 min before the addition of a solution of 8-bromomethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (200 mg, 0.44 mmol) in DMF (2 mL). The resulting mixture was stirred at r.t. for 72 h, then partitioned between DCM and H2O. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient acetonitrile 30-70%) affording 711 as a white solid (22 mg, 15%). LCMS: RT 2.43 min, [M+H]+ 518.2. 1H NMR (DMSO, 400 MHz): δ 8.01-8.01 (1 H, m), 7.63-7.62 (1 H, m), 7.25-7.24 (2 H, m), 4.83 (2 H, s), 4.26 (4 H, brd s), 3.77 (4 H, t, J=4.61 Hz), 3.74 (3 H, s), 3.31 (2 H, m), 3.26 (2 H, q, J=7.45 Hz), 3.15 (2 H, s), 2.69-2.68 (3 H, m), 1.33 (3 H, t, J=7.44 Hz), 0.98 (6 H, d, J=6.50 Hz) partitioned between DCM and H2O The organic phase was dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%)

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

実験手順: To a solution 4-isopropylpiperazin-2-one (56 mg, 0.35 mmol) in DMF (3 mL) at 0° C. was added sodium hydride (18 mg, 0.45 mmol, 60% dispersion in mineral oil) and the resulting mixture stirred for 30 min before the addition of a solution of 8-bromomethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (200 mg, 0.44 mmol) in DMF (2 mL). The resulting mixture was stirred at r.t. for 72 h, then partitioned between DCM and H2O. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient acetonitrile 30-70%) affording 711 as a white solid (22 mg, 15%). LCMS: RT 2.43 min, [M+H]+518.2. 1H NMR (DMSO, 400 MHz): δ 8.01-8.01 (1 H, m), 7.63-7.62 (1 H, m), 7.25-7.24 (2 H, m), 4.83 (2 H, s), 4.26 (4 H, brd s), 3.77 (4 H, t, J=4.61 Hz), 3.74 (3 H, s), 3.31 (2 H, m), 3.26 (2 H, q, J=7.45 Hz), 3.15 (2 H, s), 2.69-2.68 (3 H, m), 1.33 (3 H, t, J=7.44 Hz), 0.98 (6 H, d, J=6.50 Hz) partitioned between DCM and H2O The organic phase was dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of piperazin-2-one (1, 0.5 g, 5 mmol) and acetone (0.58 g, 10 mmol) in 1,2-dichloroethane (20 mL) was added sodium triacetoxyborohydride (3.18 g, 15.0 mmol) and the mixture was heated at 70° C. for 2 h. The mixture was diluted with EtOAc/saturated Na2CO3 (100/50 mL), washed with brine (20 mL), dried (Na2SO4), filtered and concentrated to afford the crude title compound (0.56 g, 79%). washed with brine (20 mL) dried (Na2SO4) filtered concentrated

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

実験手順: To a solution of 4-isopropyl-piperazin-2-one (32 mg, 0.22 mmol) in DMF (2.2 mL) at 0° C. was added NaH (90%, 11 mg). After 30 min, a solution of [5-chloromethyl-2-(3,4-dichloro-phenoxy)-benzyl]-methyl-carbamic acid tert-butyl ester (96 mg, 0.22 mmol) in DMF (2.2 mL) was added and the reaction was allowed to come to rt and stir overnight. The mixture was quenched with satd. aq. NaHCO3 and extracted with DCM. The combined organic layers were dried (Na2SO4) and concentrated. The crude product was purified by FCC to provide the desired product (94 mg, 79%). MS (ESI): mass calcd. for C27H35Cl2N3O4, 535.20; m/z found, 536.2 [M+H]. to come to rt The mixture was quenched with satd aq. NaHCO3 and extracted with DCM The combined organic layers were dried (Na2SO4) concentrated The crude product was purified by FCC

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of piperazin-2-one (1, 0.5 g, 5 mmol) and acetone (0.58 g, 10 mmol) in 1,2-dichloroethane (20 mL) was added sodium triacetoxyborohydride (3.18 g, 15.0 mmol) and the mixture was heated at 70° C. for 2 h. The mixture was diluted with EtOAc/saturated Na2CO3 (100/50 mL), washed with brine (20 mL), dried (Na2SO4), filtered and concentrated to afford the crude title compound (0.56 g, 79%). washed with brine (20 mL) dried (Na2SO4) filtered concentrated