2,4-二氯-1-(异氰基甲基)苯

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (2,4-dichlorophenyl)methyl isocyanide (0.094 g, 0.5 mmol) and 3,3-dimethyl-4-oxobutanoic acid (0.065 mg, 0.5 mmol, prepared as described below) in methanol (2 ml) was added methylamine (0.080 ml, 33% solution in ethanol). The mixture was heated to 100° C. for 30 minutes in a microwave reactor. The solvent was removed in vacuo and the residue was purified by mass-directed automated HPLC to give a colourless gum which was triturated with diethyl ether to give N-[(2,4-dichlorophenyl)methyl]-1,3,3-trimethyl-5-oxoprolinamide (0.043 g) as a sticky white solid. The solvent was removed in vacuo the residue was purified to give a colourless gum which was triturated with diethyl ether

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (2,4-dichlorophenyl)methyl isocyanide (0.047 g, 0.25 mmol) and levulinic acid (0.041 ml, 0.4 mmol) in methanol (2 ml) was added cyclopropylamine (0.042 ml, 0.6 mmol). The mixture was heated to 100° C. for 30 minutes in a microwave reactor. The solvent was removed in vacuo and the residue was purified by mass-directed automated HPLC to give 1-cyclopropyl-N-[(2,4-dichlorophenyl)methyl]-2-methyl-5-oxoprolinamide (0.054 g) as a white solid. The solvent was removed in vacuo the residue was purified

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (2,4-Dichlorophenyl)methyl isocyanide (0.075 g, 0.4 mmol) and crude 2,2-dimethyl-4-oxobutanoic acid (0.115 g, 0.6 mmol) were dissolved in methanol (2 ml). Ethylamine solution (2M in water, 0.3 ml, 0.6 mmol) was added and the mixture was heated in a sealed vessel at 100° C. for 30 minutes in a microwave reactor. The mixture was left to stand over the weekend and then the solvent was removed in vacuo and the resulting orange oil was purified by mass-directed automated HPLC to give a clear oily gum which was triturated with diethyl ether to give N-[(2,4-dichlorophenyl)methyl]-1-ethyl-4,4-dimethyl-5-oxoprolinamide as a white solid (0.024 g). LC/MS [M+H]+=343, retention time=2.57 minutes. The mixture was left the solvent was removed in vacuo the resulting orange oil was purified to give a clear oily gum which was triturated with diethyl ether

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (2,4-dichlorophenyl)methyl isocyanide (0.047 g, 0.25 mmol) and 4-oxobutanoic acid (15% in water, 0.26 ml, 0.4 mmol) in methanol (1.75 ml) was added cyclopropylamine (0.042 ml, 0.6 mmol). The mixture was heated to 100° C. for 30 minutes in a microwave reactor. The solvent was removed in vacuo and the residue was purified by mass-directed automated HPLC to give 1-Cyclopropyl-N-[(2,4-dichlorophenyl)methyl]-5-oxoprolinamide (0.072 g) as a white solid. LC/MS [M+H]+=326/328, retention time=2.29 minutes. The solvent was removed in vacuo the residue was purified

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (2,4-dichlorophenyl)methyl isocyanide (0.047 g, 0.25 mmol) and 4-oxobutanoic acid (15% in water, 0.26 ml, 0.4 mmol) in methanol (1.75 ml) was added cyclopropylamine (0.042 ml, 0.6 mmol). The mixture was heated to 100° C. for 30 minutes in a microwave reactor. The solvent was removed in vacuo and the residue was purified by mass-directed automated HPLC to give 1-Cyclopropyl-N-[(2,4-dichlorophenyl)methyl]-5-oxoprolinamide (0.072 g) as a white solid. LC/MS [M+H]+=326/328, retention time=2.29 minutes. The solvent was removed in vacuo the residue was purified

反应条件: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of methylglyoxal (0.153 ml, 1 mmol) in methanol (2 ml) was added cyclopropylamine (0.069 ml, 1 mmol). After stirring at 22° C. for 5 minutes the mixture was treated with [bis(ethyloxy)phosphoryl]acetic acid (0.161 ml, 1 mmol) and (2,4-dichlorophenyl)methyl isocyanide (0.188 g, 1 mmol). The mixture was then stirred for a further 18 hrs at 22° C. following which the solvent was removed in vacuo and the resulting residue was purified by mass-directed automated HPLC to give diethyl (2-{cyclopropyl[1-({[(2,4-dichlorophenyl)methyl]amino}-carbonyl)-2-oxopropyl]amino}-2-oxoethyl)phosphonate (0.043 g) as a brown gum. The mixture was then stirred for a further 18 hrs at 22° C. was removed in vacuo the resulting residue was purified

反应条件: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of methylglyoxal (0.153 ml, 1 mmol) in methanol (2 ml) was added cyclopropylamine (0.069 ml, 1 mmol). After stirring at 22° C. for 5 minutes the mixture was treated with [bis(ethyloxy)phosphoryl]acetic acid (0.161 ml, 1 mmol) and (2,4-dichlorophenyl)methyl isocyanide (0.188 g, 1 mmol). The mixture was then stirred for a further 18 hrs at 22° C. following which the solvent was removed in vacuo and the resulting residue was purified by mass-directed automated HPLC to give diethyl (2-{cyclopropyl[1-({[(2,4-dichlorophenyl)methyl]amino}-carbonyl)-2-oxopropyl]amino}-2-oxoethyl)phosphonate (0.043 g) as a brown gum. The mixture was then stirred for a further 18 hrs at 22° C. was removed in vacuo the resulting residue was purified

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (2,4-dichlorophenyl)methyl isocyanide (0.094 g, 0.5 mmol) and 3,3-dimethyl-4-oxobutanoic acid (0.065 mg, 0.5 mmol, prepared as described below) in methanol (2 ml) was added methylamine (0.080 ml, 33% solution in ethanol). The mixture was heated to 100° C. for 30 minutes in a microwave reactor. The solvent was removed in vacuo and the residue was purified by mass-directed automated HPLC to give a colourless gum which was triturated with diethyl ether to give N-[(2,4-dichlorophenyl)methyl]-1,3,3-trimethyl-5-oxoprolinamide (0.043 g) as a sticky white solid. The solvent was removed in vacuo the residue was purified to give a colourless gum which was triturated with diethyl ether

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (2,4-dichlorophenyl)methyl isocyanide (0.094 g, 0.5 mmol) and 3,3-dimethyl-4-oxobutanoic acid (0.065 mg, 0.5 mmol, prepared as described below) in methanol (2 ml) was added methylamine (0.080 ml, 33% solution in ethanol). The mixture was heated to 100° C. for 30 minutes in a microwave reactor. The solvent was removed in vacuo and the residue was purified by mass-directed automated HPLC to give a colourless gum which was triturated with diethyl ether to give N-[(2,4-dichlorophenyl)methyl]-1,3,3-trimethyl-5-oxoprolinamide (0.043 g) as a sticky white solid. The solvent was removed in vacuo the residue was purified to give a colourless gum which was triturated with diethyl ether

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (2,4-dichlorophenyl)methyl isocyanide (0.047 g, 0.25 mmol) and levulinic acid (0.041 ml, 0.4 mmol) in methanol (2 ml) was added cyclopropylamine (0.042 ml, 0.6 mmol). The mixture was heated to 100° C. for 30 minutes in a microwave reactor. The solvent was removed in vacuo and the residue was purified by mass-directed automated HPLC to give 1-cyclopropyl-N-[(2,4-dichlorophenyl)methyl]-2-methyl-5-oxoprolinamide (0.054 g) as a white solid. The solvent was removed in vacuo the residue was purified

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (2,4-dichlorophenyl)methyl isocyanide (0.047 g, 0.25 mmol) and levulinic acid (0.041 ml, 0.4 mmol) in methanol (2 ml) was added cyclopropylamine (0.042 ml, 0.6 mmol). The mixture was heated to 100° C. for 30 minutes in a microwave reactor. The solvent was removed in vacuo and the residue was purified by mass-directed automated HPLC to give 1-cyclopropyl-N-[(2,4-dichlorophenyl)methyl]-2-methyl-5-oxoprolinamide (0.054 g) as a white solid. The solvent was removed in vacuo the residue was purified

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (2,4-Dichlorophenyl)methyl isocyanide (0.075 g, 0.4 mmol) and crude 2,2-dimethyl-4-oxobutanoic acid (0.115 g, 0.6 mmol) were dissolved in methanol (2 ml). Ethylamine solution (2M in water, 0.3 ml, 0.6 mmol) was added and the mixture was heated in a sealed vessel at 100° C. for 30 minutes in a microwave reactor. The mixture was left to stand over the weekend and then the solvent was removed in vacuo and the resulting orange oil was purified by mass-directed automated HPLC to give a clear oily gum which was triturated with diethyl ether to give N-[(2,4-dichlorophenyl)methyl]-1-ethyl-4,4-dimethyl-5-oxoprolinamide as a white solid (0.024 g). LC/MS [M+H]+=343, retention time=2.57 minutes. The mixture was left the solvent was removed in vacuo the resulting orange oil was purified to give a clear oily gum which was triturated with diethyl ether