2-methylpropanimidamide

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: The intermediate, 6-(chloromethyl)-2-(1-methylethyl)-4(1H)pyrimidinone, was prepared according to Swiss patent 524617 from ethyl 4-chloroacetoacetate and isobutyramidine. m.p. 123°-125°. The intermediate chloromethyl compound (25 g) was stirred with 50 ml methanol at room temperature. To this mixture was added, dropwise, a solution of 25 g ammonium dimethyl phosphorodithioate dissolved in 500 ml methanol. The mixture was then heated to reflux for 6 hours, then the solvent was evaporated under reduced pressure yielding a solid. The solid was dissolved in dichloromethane and washed with water, separated, dried, and the solvent was evaporated. The remaining solid was recrystallized from toluene; yield: 15.9 g, m.p. 89°-93°. To this mixture was added The mixture was then heated to reflux for 6 hours the solvent was evaporated under reduced pressure yielding a solid washed with water separated dried the solvent was evaporated The remaining solid was recrystallized from toluene

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

実験手順: The intermediate, 6-(chloromethyl)-2-(1-methylethyl)-4(1H)pyrimidinone, was prepared according to Swiss patent 524617 from ethyl 4-chloroacetoacetate and isobutyramidine. m.p. 123°-125°. The intermediate chloromethyl compound (25 g) was stirred with 50 ml methanol at room temperature. To this mixture was added, dropwise, a solution of 25 g ammonium dimethyl phosphorodithioate dissolved in 500 ml methanol. The mixture was then heated to reflux for 6 hours, then the solvent was evaporated under reduced pressure yielding a solid. The solid was dissolved in dichloromethane and washed with water, separated, dried, and the solvent was evaporated. The remaining solid was recrystallized from toluene; yield: 15.9 g, m.p. 89°-93°. To this mixture was added The mixture was then heated to reflux for 6 hours the solvent was evaporated under reduced pressure yielding a solid washed with water separated dried the solvent was evaporated The remaining solid was recrystallized from toluene

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

実験手順: 3-(ethyloxy)-2-cyclohexen-1-one (1000 g, 1.0 eq, 1.0 wt) was dissolved in acetonitrile (5 L, 5 vol) at 0° C. and N-bromosuccinimide (1295 g, 1.02 eq, 1.295 wt) was added in four equal portions over 1 hour at <5° C. The mixture was stirred for 15 minutes at 0° C., warmed to 20° C. and stirred for a further 15 minutes at this temperature and sampled for completion by HPLC. Reaction was complete. 2-methylpropanimidamide (981 g, 1.1 eq, 0.981 wt) was added and the mixture stirred for 5 minutes at 20° C. Anhydrous sodium carbonate (1134 g, 1.5 eq, 1.134 wt) was charged to the vessel and the contents warmed to 65° C., stirred for a further 2 hours and sampled for completion by HPLC. Reaction was complete. Water (7 L, 7 vol) was added at 60° C. and the contents stirred for a further 15 minutes. 2-methyltetrahydrofuran (7 L, 7 vol) was added at 50° C. The suspension was cooled to 25° C., filtered and the inorganic solids washed with 2-methyltetrahydrofuran (2 L, 2 vol). The biphase was stirred for 5 minutes, settled and separated. The aqueous phase was back-extracted with 2-methyltetrahydrofuran (5 L, 5 vol). The combined organic phases were concentrated by atmospheric distillation to 5 L/5 vol. Toluene (10 L, 10 vol) was added, the mixture was concentrated by atmospheric distillation to 5 L/5 vol and cooled to 60° C. 5-6M hydrochloric acid in propan-2-ol (2 L, 1.3 eq, 2 vol) was added over 35 minutes at 60° C. Crystallisation was observed towards the end of the addition. The slurry was aged at 60° C. for 1 hour, cooled to 0° C. over 4 hours and stirred at this temperature for 10 hours 45 minutes. Solids were collected by vacuum filtration, washed with chilled (5° C.) toluene/propan-2-ol (2×2.5 L, 2:1 v/v, 2×2.5 vol), followed by tert-butylmethylether (2×2.5 L, 2×2.5 vol) and dried in vacuo at 50° C. for 5 hours. Yield of title compound obtained was 887 g, however this contained 13.2% w/w succinic acid and 4.2% w/w inorganics. Corrected yield was therefore 736 g/48% theory yield/74% w/w yield. warmed to 20° C. stirred for a further 15 minutes at this temperature sampled for completion by HPLC Reaction the mixture stirred for 5 minutes at 20° C the contents warmed to 65° C. stirred for a further 2 hours sampled for completion by HPLC Reaction the contents stirred for a further 15 minutes The suspension was cooled to 25° C. filtered the inorganic solids washed with 2-methyltetrahydrofuran (2 L, 2 vol) The biphase was stirred for 5 minutes separated The aqueous phase was back-extracted with 2-methyltetrahydrofuran (5 L, 5 vol) The combined organic phases were concentrated by atmospheric distillation to 5 L/5 vol. Toluene (10 L, 10 vol) was added the mixture was concentrated by atmospheric distillation to 5 L/5 vol cooled to 60° C Crystallisation was observed towards the end of the addition The slurry was aged at 60° C. for 1 hour cooled to 0° C. over 4 hours stirred at this temperature for 10 hours 45 minutes Solids were collected by vacuum filtration washed with chilled (5° C.) toluene/propan-2-ol (2×2.5 L, 2:1 v/v, 2×2.5 vol) dried in vacuo at 50° C. for 5 hours

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

実験手順: The intermediate, 6-(chloromethyl)-2-(1-methylethyl)-4(1H)pyrimidinone, was prepared according to Swiss patent 524617 from ethyl 4-chloroacetoacetate and isobutyramidine. m.p. 123°-125°. The intermediate chloromethyl compound (25 g) was stirred with 50 ml methanol at room temperature. To this mixture was added, dropwise, a solution of 25 g ammonium dimethyl phosphorodithioate dissolved in 500 ml methanol. The mixture was then heated to reflux for 6 hours, then the solvent was evaporated under reduced pressure yielding a solid. The solid was dissolved in dichloromethane and washed with water, separated, dried, and the solvent was evaporated. The remaining solid was recrystallized from toluene; yield: 15.9 g, m.p. 89°-93°. To this mixture was added The mixture was then heated to reflux for 6 hours the solvent was evaporated under reduced pressure yielding a solid washed with water separated dried the solvent was evaporated The remaining solid was recrystallized from toluene