1-ethylpiperazin-2-one

反応条件: temp:70.01; pressure:0.00; stir:

実験手順: Dilution of the aliquot (2 uL) with DMSO (200 uL).

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: 1-Ethyl-2-oxopiperazine (3TFA salt, 10.5 g) was dissolved in acetonitrile (200 ml), and N,N-diisopropylethylamine (19.5 ml) followed by 3,4-difluoronitrobenzene (2.25 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-ethyl-3-oxopiperazin-1-yl)nitrobenzene as a solid (3.44 g). were added The mixture was heated to reflux for 18 hours Solvent was evaporated the residue chromatographed on silica using as eluant 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-ethyl-3-oxopiperazine (5.9 g) was dissolved in dichloromethane (100 ml), 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-ethyl-2-oxopiperazine product as a salt with 3 moles of trifluoroacetic acid. cooled in an ice-bath Solvent was evaporated

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyrimidin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate (15.0 mg, 0.029 mmol) in DMF (0.4 mL) was added 1-ethylpiperazin-2-one (7.4 mg, 0.058 mmol). The reaction mixture was heated at 100° C. overnight. Reaction mixture was concentrated in vacuo and purified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes) to give the product. LCMS-ESI+: calc'd for C31H35ClN5O4S: 608.2 (M+H+); Found: 608.2 (M+H+). Reaction mixture was concentrated in vacuo purified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes) to give the product

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:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: DIPEA (0.219 mL, 1.23 mmol) was added to 2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl methanesulfonate (200 mg, 0.41 mmol) and 1-ethylpiperazin-2-one (52.6 mg, 0.41 mmol) in DMF (5 mL) at 20° C. under nitrogen. The resulting solution was stirred at 110° C. for 3 hours and the solvent was removed in vacuo to give an orange gum, which was dissolved in DCM (100 mL) and the solution washed with water (100 mL). The organic layer was passed through a phase separating cartridge and then evaporated to dryness to give an orange gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% EtOAc in isohexane then 10% methanolic ammonia in EtOAc. Pure fractions were evaporated to dryness to afford a yellow gum, which was triturated with ether to give 1-ethyl-4-[2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-one (77 mg, 36.1%) as a white solid. the solvent was removed in vacuo to give an orange gum, which the solution washed with water (100 mL) separating cartridge evaporated to dryness to give an orange gum The crude product was purified by flash silica chromatography, elution gradient 0 to 10% EtOAc in isohexane Pure fractions were evaporated to dryness to afford a yellow gum, which was triturated with ether

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

実験手順: From 2-bromo-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamide with cesium carbonate and 1-ethyl-piperazin-2-one. ES-MS m/e (%):519 (M+Na+, 28), 497 (M+H30 , 100).

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

実験手順: 1-Ethyl-2-oxopiperazine (3TFA salt, 10.5 g) was dissolved in acetonitrile (200 ml), and N,N-diisopropylethylamine (19.5 ml) followed by 3,4-difluoronitrobenzene (2.25 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-ethyl-3-oxopiperazin-1-yl)nitrobenzene as a solid (3.44 g). were added The mixture was heated to reflux for 18 hours Solvent was evaporated the residue chromatographed on silica using as eluant 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