1-(2-methoxyethyl)piperazin-2-one

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: 1-(2-Methoxyethyl)-2-oxopiperazine (4TFA salt, 13.5 g) was dissolved in acetonitrile (200 ml), and N,N-diisopropylethylamine (22.6 ml) followed by 3,4-difluoronitrobenzene (2.2 ml) were added. The mixture was heated to reflux for 18 hours. Solvent was evaporated, and the residue chromatographed on silica, using as eluant a gradient increasing in polarity from 0 to 4% methanol in dichloromethane. Relevant fractions were combined and evaporated to give a solid containing some N,N-diisopropylethylamine trifluoroacetate. The solid was purified by dissolving in ethyl acetate and washing well with water. Evaporation of the organic layer gave 3-fluoro-4-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)nitrobenzene as a solid (4.07 g). were added The mixture was heated to reflux for 18 hours Solvent was evaporated the residue chromatographed on silica a gradient increasing in polarity from 0 to 4% methanol in dichloromethane evaporated to give a solid The solid was purified by dissolving in ethyl acetate washing well with water Evaporation of the organic layer

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

実験手順: 1-tert-Butoxycarbonyl-4-(2-methoxyethyl)-3-oxopiperazine (6.6 g) was dissolved in dichloromethane (100 ml), the resulting solution cooled in an ice-bath, and trifluoroacetic acid (145 ml) added. The mixture was stirred at the same temperature for 2 hours. Solvent was evaporated to yield 1-(2-methoxyethyl)-2-oxopiperazine product as a salt with 4 moles of trifluoroacetic acid. the resulting solution cooled in an ice-bath Solvent was evaporated

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

実験手順: 1-tert-Butoxycarbonyl-4-(2-methoxyethyl)-3-oxopiperazine (6.6 g) was dissolved in dichloromethane (100 ml), the resulting solution cooled in an ice-bath, and trifluoroacetic acid (145 ml) added. The mixture was stirred at the same temperature for 2 hours. Solvent was evaporated to yield 1-(2-methoxyethyl)-2-oxopiperazine product as a salt with 4 moles of trifluoroacetic acid. the resulting solution cooled in an ice-bath Solvent was evaporated

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: The crude product obtained using (E)-4-[2-(1H-indazol-3-yl)vinyl]benzoic acid (50.0 mg, 0.189 mmol) obtained in Step 6 of Example 1, N-methylmorpholine (0.0415 mL, 0.378 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (50.7 mg, 0.265 mmol), 1-hydroxybenzotriazole monohydrate (33.2 mg, 0.246 mmol) and 1-(2-methoxyethyl)piperazin-2-one (44.8 mg, 0.284 mmol) in a similar manner to Step 7 of Example 1, was treated with hydrogen chloride-ethyl acetate solution (4 mol/L, 0.236 mL) to obtain Compound 134 (10.0 mg, 12%).

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

実験手順: The crude product obtained using (E)-4-[2-(1H-indazol-3-yl)vinyl]benzoic acid (50.0 mg, 0.189 mmol) obtained in Step 6 of Example 1, N-methylmorpholine (0.0415 mL, 0.378 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (50.7 mg, 0.265 mmol), 1-hydroxybenzotriazole monohydrate (33.2 mg, 0.246 mmol) and 1-(2-methoxyethyl)piperazin-2-one (44.8 mg, 0.284 mmol) in a similar manner to Step 7 of Example 1, was treated with hydrogen chloride-ethyl acetate solution (4 mol/L, 0.236 mL) to obtain Compound 134 (10.0 mg, 12%).

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

実験手順: 1-(2-Methoxyethyl)-2-oxopiperazine (4TFA salt, 13.5 g) was dissolved in acetonitrile (200 ml), and N,N-diisopropylethylamine (22.6 ml) followed by 3,4-difluoronitrobenzene (2.2 ml) were added. The mixture was heated to reflux for 18 hours. Solvent was evaporated, and the residue chromatographed on silica, using as eluant a gradient increasing in polarity from 0 to 4% methanol in dichloromethane. Relevant fractions were combined and evaporated to give a solid containing some N,N-diisopropylethylamine trifluoroacetate. The solid was purified by dissolving in ethyl acetate and washing well with water. Evaporation of the organic layer gave 3-fluoro-4-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)nitrobenzene as a solid (4.07 g). were added The mixture was heated to reflux for 18 hours Solvent was evaporated the residue chromatographed on silica a gradient increasing in polarity from 0 to 4% methanol in dichloromethane evaporated to give a solid The solid was purified by dissolving in ethyl acetate washing well with water Evaporation of the organic layer

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

実験手順: 1-tert-Butoxycarbonyl-4-(2-methoxyethyl)-3-oxopiperazine (6.6 g) was dissolved in dichloromethane (100 ml), the resulting solution cooled in an ice-bath, and trifluoroacetic acid (145 ml) added. The mixture was stirred at the same temperature for 2 hours. Solvent was evaporated to yield 1-(2-methoxyethyl)-2-oxopiperazine product as a salt with 4 moles of trifluoroacetic acid. the resulting solution cooled in an ice-bath Solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir: