1-butylimidazolidine-2,4-dione

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1-Butyl-2,4-imidazolidinedione (0.600 g, 4.17 mmol) in THF (15ml) at -78° C. is added lithium diisopropylamide (2.1 equiv.). After stirring for 20 minutes a solution of methyl 4-[(2-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoate (1.250 g, 4.17 mmol) in THF (10 mL) is added dropwise over 10 minutes to form an orange solution. This solution is stirred for a further 20 minutes at -78° C. and is then added to aqueous ammonium chloride. This mixture is evaporated in vacuo and then extracted into ethyl acetate. After washing with water and then brine the solution is dried over Na2SO4. Evaporation in vacuo and chromatography, eluant 5% methanol in chloroform, affords the required product. Recrystallized from ethyl acetate containing traces of methanol. is added dropwise over 10 minutes to form an orange solution This mixture is evaporated in vacuo extracted into ethyl acetate After washing with water brine the solution is dried over Na2SO4 Evaporation in vacuo and chromatography, eluant 5% methanol in chloroform

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

Procedure: A quantity of 24.4 g (0.30 mole) of potassium cyanate is added portionwise, at room temperature, to a stirred solution of 31.80 g (0.20 mole) of ethyl N-butylglycinate in 220 mL (0.22 mole) of 1N hydrochloric acid. The solution is warmed to ca. 90° C. (at ca. 50° C. an oil separates). After 10 minutes at 90° C., concentrated hydrochloric acid (250 mL) is cautiously added over 2 minutes and the resulting solution is heated at 90°-100° C. for 1/2 hour. The solution is concentrated at reduced pressure to dryness. The last amounts of water are chased by addition and removal of 3×100 mL of absolute ethanol. The residue is extracted with 400 mL 50% ethanolmethylene chloride. The inorganics are filtered and the filtrate is concentrated to dryness. Trituration of the residue with 100 mL of water and filtration gives pure 1-butylhydantoin in 68% yield; mp 90°-92° C.; MS (EI) 156.1 (M+). the resulting solution is heated at 90°-100° C. for 1/2 hour The solution is concentrated at reduced pressure to dryness The last amounts of water are chased by addition and removal of 3×100 mL of absolute ethanol The residue is extracted with 400 mL 50% ethanolmethylene chloride The inorganics are filtered the filtrate is concentrated to dryness Trituration of the residue with 100 mL of water and filtration

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

Procedure: A quantity of 24.4 g (0.30 mole) of potassium cyanate is added portionwise, at room temperature, to a stirred solution of 31.80 g (0.20 mole) of ethyl N-butylglycinate in 220 mL (0.22 mole) of 1N hydrochloric acid. The solution is warmed to ca. 90° C. (at ca. 50° C. an oil separates). After 10 minutes at 90° C., concentrated hydrochloric acid (250 mL) is cautiously added over 2 minutes and the resulting solution is heated at 90°-100° C. for 1/2 hour. The solution is concentrated at reduced pressure to dryness. The last amounts of water are chased by addition and removal of 3×100 mL of absolute ethanol. The residue is extracted with 400 mL 50% ethanolmethylene chloride. The inorganics are filtered and the filtrate is concentrated to dryness. Trituration of the residue with 100 mL of water and filtration gives pure 1-butylhydantoin in 68% yield; mp 90°-92° C.; MS (EI) 156.1 (M+). the resulting solution is heated at 90°-100° C. for 1/2 hour The solution is concentrated at reduced pressure to dryness The last amounts of water are chased by addition and removal of 3×100 mL of absolute ethanol The residue is extracted with 400 mL 50% ethanolmethylene chloride The inorganics are filtered the filtrate is concentrated to dryness Trituration of the residue with 100 mL of water and filtration

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.44 g (0.012 mole) of 2-butyl-1-(4-carboxybenzyl)-5-formylimidazole, 2.40 g (0.016 mole) of 1-butylhydantoin, 25.92 g (0.071 mole) of 25% tetramethylammonium hydroxide-in-methanol and 12 mL of water is heated with stirring with an oil bath (bath temperature 135°-150° C.), allowing the methanol to distill over. After ca. 1/2 hour, the pot temperature is ca. 115°-120° C. The temperature is maintained 115°-120° C. for 15 minutes. The reaction solution is cooled to 70° C. and 5.04 g (0.084 mole) of glacial acetic acid and then ca. 100 mL of water are added to precipitate the mixed cis (Z) and trans (E) isomers. Separation with 200 mL of methanol, cooling, and filtering off the least soluble (E) isomer. Recrystallization of the (E) isomer is effected by dissolution in 50% methanol-methylene chloride and concentration to remove methylene chloride. The separated pale yellow crystals are filtered; mp 287°-289° C.; tlc (2:10 MeOH--CHCl3), 1 spot, Rf 0.4; nmr (DMSO--d6), vinyl proton at δ 5.86 ppm; MS (CI) 425.1 (M+ +1). to distill over is ca. 115°-120° C The temperature is maintained 115°-120° C. for 15 minutes to precipitate the mixed cis (Z) and trans (E) Separation with 200 mL of methanol cooling filtering off the least soluble (E) isomer Recrystallization of the (E) isomer is effected by dissolution in 50% methanol-methylene chloride concentration to remove methylene chloride The separated pale yellow crystals are filtered

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.44 g (0.012 mole) of 2-butyl-1-(4-carboxybenzyl)-5-formylimidazole, 2.40 g (0.016 mole) of 1-butylhydantoin, 25.92 g (0.071 mole) of 25% tetramethylammonium hydroxide-in-methanol and 12 mL of water is heated with stirring with an oil bath (bath temperature 135°-150° C.), allowing the methanol to distill over. After ca. 1/2 hour, the pot temperature is ca. 115°-120° C. The temperature is maintained 115°-120° C. for 15 minutes. The reaction solution is cooled to 70° C. and 5.04 g (0.084 mole) of glacial acetic acid and then ca. 100 mL of water are added to precipitate the mixed cis (Z) and trans (E) isomers. Separation with 200 mL of methanol, cooling, and filtering off the least soluble (E) isomer. Recrystallization of the (E) isomer is effected by dissolution in 50% methanol-methylene chloride and concentration to remove methylene chloride. The separated pale yellow crystals are filtered; mp 287°-289° C.; tlc (2:10 MeOH--CHCl3), 1 spot, Rf 0.4; nmr (DMSO--d6), vinyl proton at δ 5.86 ppm; MS (CI) 425.1 (M+ +1). to distill over is ca. 115°-120° C The temperature is maintained 115°-120° C. for 15 minutes to precipitate the mixed cis (Z) and trans (E) Separation with 200 mL of methanol cooling filtering off the least soluble (E) isomer Recrystallization of the (E) isomer is effected by dissolution in 50% methanol-methylene chloride concentration to remove methylene chloride The separated pale yellow crystals are filtered

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

Procedure: 1-Butylimidazolidine-2,4-dione (100 mg, 0.64 mmol) and 1-isocyanatoheptane (108.5 mg, 0.768 mmol) were reacted in DMF in analogy to example 1. Yield: 15 mg (8%), M+H+: 298.18.

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

Procedure: 1-Butylimidazolidine-2,4-dione (100 mg, 0.64 mmol) and 1-isocyanatohexane (97.7 mg, 0.768 mmol) were reacted in DMF in analogy to example 1. Yield: 9 mg (5%), M+H+: 284.50.

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

Procedure: 1-Butylimidazolidine-2,4-dione (100 mg, 0.64 mmol) and 1-isocyanatohexane (97.7 mg, 0.768 mmol) were reacted in DMF in analogy to example 1. Yield: 9 mg (5%), M+H+: 284.50.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1-butyl-2,4-imidazolidinedione (0.600 g, 4.17 mmol) in THF (15 ml) at -78° C. is added lithium diisopropylamide (2.1 equiv.). After stirring for 20 minutes a solution of methyl 4-[(2-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoate (1.250 g, 4.17 mmol) in THF (10 mL) is added dropwise over 10 minutes to form an orange solution. This solution is stirred for a further 20 minutes at -78° C. and is then added to aqueous ammonium chloride. This mixture is evaporated in vacuo and then extracted into ethyl acetate. After washing with water and then brine the solution is dried over Na2SO4. Evaporation in vacuo and chromatography, eluant 5% methanol in chloroform, affords the required product. Recrystallized from ethyl acetate containing traces of methanol. is added dropwise over 10 minutes to form an orange solution This mixture is evaporated in vacuo extracted into ethyl acetate After washing with water brine the solution is dried over Na2SO4 Evaporation in vacuo and chromatography, eluant 5% methanol in chloroform

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

Procedure: A quantity of 24.4 g (0.30 mole) of potassium cyanate is added portionwise, at room temperature, to a stirred solution of 31.80 g (0.20 mole) of ethyl N-butylglycinate in 220 mL (0.22 mole) of 1 N hydrochloric acid. The solution is warmed to ca. 90° C. (at ca. 50° C. an oil separates). After 10 minutes at 90° C., concentrated hydrochloric acid (250 mL) is cautiously added over 2 minutes and the resulting solution is heated at 90°100° C. for 1/2 hour. The solution is concentrated at reduced pressure to dryness. The last amounts of water are chased by addition and removal of 3×100 mL of absolute ethanol. The residue is extracted with 400 mL 50% ethanol-methylene chloride. The inorganics are filtered and the filtrate is concentrated to dryness. Trituration of the residue with 100 mL of water and filtration gives pure 1-butylhydantoin in 68% yield; mp 90°92° C.; MS (EI) 156.1 (M+). the resulting solution is heated at 90°100° C. for 1/2 hour The solution is concentrated at reduced pressure to dryness The last amounts of water are chased by addition and removal of 3×100 mL of absolute ethanol The residue is extracted with 400 mL 50% ethanol-methylene chloride The inorganics are filtered the filtrate is concentrated to dryness Trituration of the residue with 100 mL of water and filtration

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1-Butyl-2,4-imidazolidinedione (0.600 g, 4.17 mmol) in THF (15ml) at -78° C. is added lithium diisopropylamide (2.1 equiv.). After stirring for 20 minutes a solution of methyl 4-[(2-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoate (1.250 g, 4.17 mmol) in THF (10 mL) is added dropwise over 10 minutes to form an orange solution. This solution is stirred for a further 20 minutes at -78° C. and is then added to aqueous ammonium chloride. This mixture is evaporated in vacuo and then extracted into ethyl acetate. After washing with water and then brine the solution is dried over Na2SO4. Evaporation in vacuo and chromatography, eluant 5% methanol in chloroform, affords the required product. Recrystallized from ethyl acetate containing traces of methanol. is added dropwise over 10 minutes to form an orange solution This mixture is evaporated in vacuo extracted into ethyl acetate After washing with water brine the solution is dried over Na2SO4 Evaporation in vacuo and chromatography, eluant 5% methanol in chloroform

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

Procedure: A quantity of 24.4 g (0.30 mole) of potassium cyanate is added portionwise, at room temperature, to a stirred solution of 31.80 g (0.20 mole) of ethyl N-butylglycinate in 220 mL (0.22 mole) of 1N hydrochloric acid. The solution is warmed to ca. 90° C. (at ca. 50° C. an oil separates). After 10 minutes at 90° C., concentrated hydrochloric acid (250 mL) is cautiously added over 2 minutes and the resulting solution is heated at 90°-100° C. for 1/2 hour. The solution is concentrated at reduced pressure to dryness. The last amounts of water are chased by addition and removal of 3×100 mL of absolute ethanol. The residue is extracted with 400 mL 50% ethanolmethylene chloride. The inorganics are filtered and the filtrate is concentrated to dryness. Trituration of the residue with 100 mL of water and filtration gives pure 1-butylhydantoin in 68% yield; mp 90°-92° C.; MS (EI) 156.1 (M+). the resulting solution is heated at 90°-100° C. for 1/2 hour The solution is concentrated at reduced pressure to dryness The last amounts of water are chased by addition and removal of 3×100 mL of absolute ethanol The residue is extracted with 400 mL 50% ethanolmethylene chloride The inorganics are filtered the filtrate is concentrated to dryness Trituration of the residue with 100 mL of water and filtration