(E)-pent-2-enoyl chloride

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

Procedure: 2-Methyl-4-piperazin-1-yl-quinoline (113.7 mg, 0.5 mmol) was dissolved in anhydrous dichloromethane (1 ml), TEA (77 μl, 0.5 mmol) followed by (E)-pent-2-enoyl chloride (65 mg, 0.55 mmol dissolved in 1 ml anhydrous dichloromethane) were added and the mixture was shaken for 15 minutes. The mixture was diluted with dichloromethane, washed with 5% sodium bicarbonate solution and water and the organic phase was evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 143 mg of a solid (0.44 mmol, 88%). MS (ES): m/z=354.2 [M+1]+. were added washed with 5% sodium bicarbonate solution and water the organic phase was evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile)

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

Procedure: 5-Methoxy-7-piperazin-1-yl-pyrazolo[1,5-a]pyrimidine (23.3 mg, 0.1 mmol) was dissolved in anhydrous dichloromethane (1 ml), TEA (17.4 μl, 1.25 mmol) followed by (E)-pent-2-enoyl chloride (14.8 mg, 0.125 mmol) were added, the mixture was shaken for 10 minutes, diluted with dichloromethane, washed with 10% sodium bicarbonate solution, water and the organic phase was evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 16.1 mg of a solid (0.05 mmol, 51%). were added washed with 10% sodium bicarbonate solution, water the organic phase was evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile)

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

Procedure: 8-Methyl-4-piperazin-1-yl-quinoline (22.7 mg, 0.1 mmol) was dissolved in dichloromethane (1 ml), triethylamine was added (1 ml of a 0.12 M solution in dichloromethane) followed by a solution of (E)-pent-2-enoyl chloride (1 ml, 0.12 M in dichloromethane). The mixture was shaken briefly, washed with 5% sodium bicarbonate solution (2×), water and evaporated to dryness. The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile) to yield 2.8 mg of a solid (0.009 mmol, 9%). washed with 5% sodium bicarbonate solution (2×), water evaporated to dryness The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)

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

Procedure: 2-Methyl-4-piperazin-1-yl-quinoline (113.7 mg, 0.5 mmol) was dissolved in anhydrous dichloromethane (1 ml), TEA (77 μl, 0.5 mmol) followed by (E)-pent-2-enoyl chloride (65 mg, 0.55 mmol dissolved in 1 ml anhydrous dichloromethane) were added and the mixture was shaken for 15 minutes. The mixture was diluted with dichloromethane, washed with 5% sodium bicarbonate solution and water and the organic phase was evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 143 mg of a solid (0.44 mmol, 88%). MS (ES): m/z=354.2 [M+1]+. were added washed with 5% sodium bicarbonate solution and water the organic phase was evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile)

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

Procedure: 5-Methoxy-7-piperazin-1-yl-pyrazolo[1,5-a]pyrimidine (23.3 mg, 0.1 mmol) was dissolved in anhydrous dichloromethane (1 ml), TEA (17.4 μl, 1.25 mmol) followed by (E)-pent-2-enoyl chloride (14.8 mg, 0.125 mmol) were added, the mixture was shaken for 10 minutes, diluted with dichloromethane, washed with 10% sodium bicarbonate solution, water and the organic phase was evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 16.1 mg of a solid (0.05 mmol, 51%). were added washed with 10% sodium bicarbonate solution, water the organic phase was evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile)

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

Procedure: 5-Methoxy-7-piperazin-1-yl-pyrazolo[1,5-a]pyrimidine (23.3 mg, 0.1 mmol) was dissolved in anhydrous dichloromethane (1 ml), TEA (17.4 μl, 1.25 mmol) followed by (E)-pent-2-enoyl chloride (14.8 mg, 0.125 mmol) were added, the mixture was shaken for 10 minutes, diluted with dichloromethane, washed with 10% sodium bicarbonate solution, water and the organic phase was evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 16.1 mg of a solid (0.05 mmol, 51%). were added washed with 10% sodium bicarbonate solution, water the organic phase was evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile)

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

Procedure: 8-Methyl-4-piperazin-1-yl-quinoline (22.7 mg, 0.1 mmol) was dissolved in dichloromethane (1 ml), triethylamine was added (1 ml of a 0.12 M solution in dichloromethane) followed by a solution of (E)-pent-2-enoyl chloride (1 ml, 0.12 M in dichloromethane). The mixture was shaken briefly, washed with 5% sodium bicarbonate solution (2×), water and evaporated to dryness. The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile) to yield 2.8 mg of a solid (0.009 mmol, 9%). washed with 5% sodium bicarbonate solution (2×), water evaporated to dryness The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-(+)-4-Phenyl-2-oxazolidinone (4.0 g, 24 mmol, Aldrich) was dissolved in dry THF (40 mL), and the solution was cooled to -50° C. and flushed with N2. Sodium hexamethyldisilazane (1.0M in THF, 25 mL, 25 mmol) was added slowly with stirring. The compound from step 7a (2.9 g, 24 mmol) was added slowly while maintaining the temperature at -50° C., and the mixture was stirred at this temperature for 1.5 hour. The mixture was allowed to warm to 0° C. and stirred for 1 hour. Saturated aqueous NH4Cl solution was added, the mixture was stirred for 10 minutes and the mixture was extracted with methylene chloride. The extract was dried over Na2SO4, filtered and the solvent was removed. The residue was chromatographed on silica gel, eluting with 2% methanol/methylene chloride, and the product was rechromatographed with 0.5% methanol/methylene chloride to give the title compound (1.69 g). MS m/ z 246 (M+H)+, 263 (M+NH4)+. flushed with N2 while maintaining the temperature at -50° C. the mixture was stirred at this temperature for 1.5 hour to warm to 0° C. stirred for 1 hour the mixture was stirred for 10 minutes the mixture was extracted with methylene chloride The extract was dried over Na2SO4 filtered the solvent was removed The residue was chromatographed on silica gel eluting with 2% methanol/methylene chloride the product was rechromatographed with 0.5% methanol/methylene chloride

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-(+)-4-Phenyl-2-oxazolidinone (4.0 g, 24 mmol, Aldrich) was dissolved in dry THF (40 mL), and the solution was cooled to -50° C. and flushed with N2. Sodium hexamethyldisilazane (1.0M in THF, 25 mL, 25 mmol) was added slowly with stirring. The compound from step 7a (2.9 g, 24 mmol) was added slowly while maintaining the temperature at -50° C., and the mixture was stirred at this temperature for 1.5 hour. The mixture was allowed to warm to 0° C. and stirred for 1 hour. Saturated aqueous NH4Cl solution was added, the mixture was stirred for 10 minutes and the mixture was extracted with methylene chloride. The extract was dried over Na2SO4, filtered and the solvent was removed. The residue was chromatographed on silica gel, eluting with 2% methanol/methylene chloride, and the product was rechromatographed with 0.5% methanol/methylene chloride to give the title compound (1.69 g). MS m/ z 246 (M+H)+, 263 (M+NH4)+. flushed with N2 while maintaining the temperature at -50° C. the mixture was stirred at this temperature for 1.5 hour to warm to 0° C. stirred for 1 hour the mixture was stirred for 10 minutes the mixture was extracted with methylene chloride The extract was dried over Na2SO4 filtered the solvent was removed The residue was chromatographed on silica gel eluting with 2% methanol/methylene chloride the product was rechromatographed with 0.5% methanol/methylene chloride

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-(+)-4-Phenyl-2-oxazolidinone (4.0 g, 24 mmol, Aldrich) was dissolved in dry THF (40 mL), and the solution was cooled to -50° C. and flushed with N2. Sodium hexamethyldisilazane (1.0M in THF, 25 mL, 25 mmol) was added slowly with stirring. The compound from step 7a (2.9 g, 24 mmol) was added slowly while maintaining the temperature at -50° C., and the mixture was stirred at this temperature for 1.5 hour. The mixture was allowed to warm to 0° C. and stirred for 1 hour. Saturated aqueous NH4Cl solution was added, the mixture was stirred for 10 minutes and the mixture was extracted with methylene chloride. The extract was dried over Na2SO4, filtered and the solvent was removed. The residue was chromatographed on silica gel, eluting with 2% methanol/methylene chloride, and the product was rechromatographed with 0.5% methanol/methylene chloride to give the title compound (1.69 g). MS m/z 246 (M+H)+, 263 (M+NH4)+. flushed with N2 while maintaining the temperature at -50° C. the mixture was stirred at this temperature for 1.5 hour to warm to 0° C. stirred for 1 hour the mixture was stirred for 10 minutes the mixture was extracted with methylene chloride The extract was dried over Na2SO4 filtered the solvent was removed The residue was chromatographed on silica gel eluting with 2% methanol/methylene chloride the product was rechromatographed with 0.5% methanol/methylene chloride

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

Procedure: 2-Methyl-4-piperazin-1-yl-quinoline (113.7 mg, 0.5 mmol) was dissolved in anhydrous dichloromethane (1 ml), TEA (77 μl, 0.5 mmol) followed by (E)-pent-2-enoyl chloride (65 mg, 0.55 mmol dissolved in 1 ml anhydrous dichloromethane) were added and the mixture was shaken for 15 minutes. The mixture was diluted with dichloromethane, washed with 5% sodium bicarbonate solution and water and the organic phase was evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 143 mg of a solid (0.44 mmol, 88%). MS (ES): m/z=354.2 [M+1]+. were added washed with 5% sodium bicarbonate solution and water the organic phase was evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile)

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

Procedure: 5-Methoxy-7-piperazin-1-yl-pyrazolo[1,5-a]pyrimidine (23.3 mg, 0.1 mmol) was dissolved in anhydrous dichloromethane (1 ml), TEA (17.4 μl, 1.25 mmol) followed by (E)-pent-2-enoyl chloride (14.8 mg, 0.125 mmol) were added, the mixture was shaken for 10 minutes, diluted with dichloromethane, washed with 10% sodium bicarbonate solution, water and the organic phase was evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 16.1 mg of a solid (0.05 mmol, 51%). were added washed with 10% sodium bicarbonate solution, water the organic phase was evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile)