methyl 2-isocyanatoacetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 70 mg (0.19 mmol) of N-{5-[4-(trifluoromethoxy)phenyl]piperidin-3-yl}benzamide were initially charged in 2.5 ml of THF, and 22 mg (0.19 mmol) of methyl N-(oxomethylidene)glycinate and 29 μl (0.21 mmol) of triethylamine were added. The mixture was stirred at RT overnight. The reaction mixture was then purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient). Yield: 76 mg (82% of theory) The reaction mixture was then purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 2.49 g quantity of carbomethoxymethylisocyanate was added to a suspension of 2.00 g of 4-hydroxy-2(1H)-pyridone in 60 ml of dioxane, and the mixture was stirred at 90° C. for 30 minutes. The solvent was distilled off, and ether was added to the residue. The precipitate thus formed was filtered, giving 2.20 g of the title compound in a yield of 54%. The solvent was distilled off ether was added to the residue The precipitate thus formed was filtered

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

Procedure: 1.40 g (8.00 mmol) of 4-chlorobenzoyl chloride, 1.00 g (10.09 mmol) of methyl isocyanatoacetate and 5.9 ml (42.39 mmol) of triethylamine are dissolved in 15 ml of dry THF and stirred at RT for 48 h. The solvent is then removed on a rotary evaporator. The residue is taken up in 20 ml of ethyl acetate and washed once with 5 ml of water. The organic phase is dried over magnesium sulfate and the solvent is removed on a rotary evaporator. The residue is suspended in 10 ml of cyclohexane and filtered off. It is then recrystallized from about 10 ml of methanol. This gives needle-shaped crystals which are dried in a drying cabinet at 50° C. A further product fraction is obtained by reprecipitation after recrystallization. The solvent is then removed on a rotary evaporator washed once with 5 ml of water The organic phase is dried over magnesium sulfate the solvent is removed on a rotary evaporator filtered off It is then recrystallized from about 10 ml of methanol This gives needle-shaped crystals which are dried in a drying cabinet at 50° C A further product fraction is obtained by reprecipitation after recrystallization

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

Procedure: 1.40 g (8.00 mmol) of 4-chlorobenzoyl chloride, 1.00 g (10.09 mmol) of methyl isocyanatoacetate and 5.9 ml (42.39 mmol) of triethylamine are dissolved in 15 ml of dry THF and stirred at RT for 48 h. The solvent is then removed on a rotary evaporator. The residue is taken up in 20 ml of ethyl acetate and washed once with 5 ml of water. The organic phase is dried over magnesium sulfate and the solvent is removed on a rotary evaporator. The residue is suspended in 10 ml of cyclohexane and filtered off. It is then recrystallized from about 10 ml of methanol. This gives needle-shaped crystals which are dried in a drying cabinet at 50° C. A further product fraction is obtained by reprecipitation after recrystallization. The solvent is then removed on a rotary evaporator washed once with 5 ml of water The organic phase is dried over magnesium sulfate the solvent is removed on a rotary evaporator filtered off It is then recrystallized from about 10 ml of methanol This gives needle-shaped crystals which are dried in a drying cabinet at 50° C A further product fraction is obtained by reprecipitation after recrystallization

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 2-(7-chloro-1,8-naphthyridin-2-yl)-3-hydroxy-isoindolin-1-one (3.2 g.), methyl 2-isocyanatoacetate (1.4 g.) and triethylamine (1.2 g.) in acetonitrile (50 cc.) is stirred for 18 hours at a temperature of about 20° C. A further amount of methyl 2-isocyanatoacetate (0.7 g.) is added and stirring is continued for a further 3 hours. The precipitate is filtered off and is dissolved in methylene chloride (35 cc.). Decolourising charcoal (0.5 g.) is added. After filtration, diisopropyl ether (105 cc.) is added to the filtrate. The crystalline precipitate which forms is filtered off, washed with diisopropyl ether (15 cc.) and then dried to give 2-(7-chloro-1,8-naphthyridin-2-yl)-3-methoxycarbonylmethylaminocarbonyloxy-isoindolin-1-one (2.5 g.) melting at 208°-210° C. stirring is continued for a further 3 hours The precipitate is filtered off is dissolved in methylene chloride (35 cc.) Decolourising charcoal (0.5 g.) is added After filtration, diisopropyl ether (105 cc.) is added to the filtrate The crystalline precipitate which forms is filtered off washed with diisopropyl ether (15 cc.) dried

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 2-(7-chloro-1,8-naphthyridin-2-yl)-3-hydroxy-isoindolin-1-one (3.2 g.), methyl 2-isocyanatoacetate (1.4 g.) and triethylamine (1.2 g.) in acetonitrile (50 cc.) is stirred for 18 hours at a temperature of about 20° C. A further amount of methyl 2-isocyanatoacetate (0.7 g.) is added and stirring is continued for a further 3 hours. The precipitate is filtered off and is dissolved in methylene chloride (35 cc.). Decolourising charcoal (0.5 g.) is added. After filtration, diisopropyl ether (105 cc.) is added to the filtrate. The crystalline precipitate which forms is filtered off, washed with diisopropyl ether (15 cc.) and then dried to give 2-(7-chloro-1,8-naphthyridin-2-yl)-3-methoxycarbonylmethylaminocarbonyloxy-isoindolin-1-one (2.5 g.) melting at 208°-210° C. stirring is continued for a further 3 hours The precipitate is filtered off is dissolved in methylene chloride (35 cc.) Decolourising charcoal (0.5 g.) is added After filtration, diisopropyl ether (105 cc.) is added to the filtrate The crystalline precipitate which forms is filtered off washed with diisopropyl ether (15 cc.) dried

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 1.40 g (8.00 mmol) of 4-chlorobenzoyl chloride, 1.00 g (10.09 mmol) of methyl isocyanatoacetate and 5.9 ml (42.39 mmol) of triethylamine are dissolved in 15 ml of dry THF and stirred at RT for 48 h. The solvent is then removed on a rotary evaporator. The residue is taken up in 20 ml of ethyl acetate and washed once with 5 ml of water. The organic phase is dried over magnesium sulfate and the solvent is removed on a rotary evaporator. The residue is suspended in 10 ml of cyclohexane and filtered off. It is then recrystallized from about 10 ml of methanol. This gives needle-shaped crystals which are dried in a drying cabinet at 50° C. A further product fraction is obtained by reprecipitation after recrystallization. The solvent is then removed on a rotary evaporator washed once with 5 ml of water The organic phase is dried over magnesium sulfate the solvent is removed on a rotary evaporator filtered off It is then recrystallized from about 10 ml of methanol This gives needle-shaped crystals which are dried in a drying cabinet at 50° C A further product fraction is obtained by reprecipitation after recrystallization

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 2-(7-chloro-1,8-naphthyridin-2-yl)-3-hydroxy-isoindolin-1-one (3.2 g.), methyl 2-isocyanatoacetate (1.4 g.) and triethylamine (1.2 g.) in acetonitrile (50 cc.) is stirred for 18 hours at a temperature of about 20° C. A further amount of methyl 2-isocyanatoacetate (0.7 g.) is added and stirring is continued for a further 3 hours. The precipitate is filtered off and is dissolved in methylene chloride (35 cc.). Decolourising charcoal (0.5 g.) is added. After filtration, diisopropyl ether (105 cc.) is added to the filtrate. The crystalline precipitate which forms is filtered off, washed with diisopropyl ether (15 cc.) and then dried to give 2-(7-chloro-1,8-naphthyridin-2-yl)-3-methoxycarbonylmethylaminocarbonyloxy-isoindolin-1-one (2.5 g.) melting at 208°-210° C. stirring is continued for a further 3 hours The precipitate is filtered off is dissolved in methylene chloride (35 cc.) Decolourising charcoal (0.5 g.) is added After filtration, diisopropyl ether (105 cc.) is added to the filtrate The crystalline precipitate which forms is filtered off washed with diisopropyl ether (15 cc.) dried