N-[(3S)-2,6-dioxooxan-3-yl]-2,2,2-trifluoroacetamide

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

Procedure: Heat at reflux for 3 hours a mixture of N-trifluoroacetyl-L-glutamic anhydride (18.0 g, 80 mmol) and AlCl3 (23.5 g, 177 mmol) in dry benzene (400 ml). Allow to cool, treat with ice (400 ml), conc. HCl (100 ml), and ethyl acetate (EtOAc) (400 ml). Dry the organic layer and concentrate to obtain the title compound as a brown crystalline solid (25 g). Heat at reflux for 3 hours Allow to cool Dry the organic layer concentrate

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Alpha-L-glutamyl-5-aminopyridine-2-carbonitrile is prepared by the method described in J. Med. Chem., 1973, 16, 163-166. A solution of 5.5 g (24.4 mmol) of N-trifluoroacetyl-L-glutamic anhydride and 2.6 g (21.8 mmol) of 2-cyano-5-aminopyridine (prepared according to tetrahydrofuran (20 cm3) is stirred for 12 h at 40° C. The solvent is then removed and the residue is dissolved in a 1% solution of sodium carbonate (80 cm3). The solution is rapidly washed with methylene chloride (3×30 cm3) and then acidified to pH 2-3 with a 6 N solution of HCl. Extraction with a solution of ethyl acetate (3×50 cm3), followed by drying over sodium sulfate and then evaporation of the solvent, gives 5.1 g of a crude product, N-trifluoroacetyl-alpha-L-glutamyl-5-aminopyridine-2-carbonitrile, which is obtained pure (melting point: 157° C.) after recrystallization several times from an ethanol/hexane mixture (40/60). After treatment of this compound with a 7.5% solution of ammonia for 4 h at 20° C., followed by concentration to dryness, alpha-L-glutamyl-5-aminopyridine-2-carbonitrile is finally obtained (quantitative yield, melting point: 152° C.). The solvent is then removed the residue is dissolved in a 1% solution of sodium carbonate (80 cm3) The solution is rapidly washed with methylene chloride (3×30 cm3) Extraction with a solution of ethyl acetate (3×50 cm3) by drying over sodium sulfate evaporation of the solvent

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

Procedure: Heat at reflux for 3 hours a mixture of N-trifluoroacetyl-L-glutamic anhydride (18.0 g, 80 mmol) and AlCl3 (23.5 g, 177 mmol) in dry benzene (400 ml). Allow to cool, treat with ice (400 ml), conc. HCl (100 ml), and ethyl acetate (EtOAc) (400 ml). Dry the organic layer and concentrate to obtain the title compound as a brown crystalline solid (25 g). Heat at reflux for 3 hours Allow to cool Dry the organic layer concentrate

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

Procedure: Heat at reflux for 3 hours a mixture of N-trifluoroacetyl-L-glutamic anhydride (18.0 g, 80 mmol) and AlCl3 (23.5 g, 177 mmol) in dry benzene (400 ml). Allow to cool, treat with ice (400 ml), conc. HCl (100 ml), and ethyl acetate (EtOAc) (400 ml). Dry the organic layer and concentrate to obtain the title compound as a brown crystalline solid (25 g). Heat at reflux for 3 hours Allow to cool Dry the organic layer concentrate

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

Procedure: Heat at reflux for 3 hours a mixture of N-trifluoroacetyl-L-glutamic anhydride (18.0 g, 80 mmol) and AlCl3 (23.5 g, 177 mmol) in dry benzene (400 ml). Allow to cool, treat with ice (400 ml), conc. HCl (100 ml), and ethyl acetate (EtOAc) (400 ml). Dry the organic layer and concentrate to obtain the title compound as a brown crystalline solid (25 g). Heat at reflux for 3 hours Allow to cool Dry the organic layer concentrate

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Alpha-L-glutamyl-5-aminopyridine-2-carbonitrile is prepared by the method described in J. Med. Chem., 1973, 16, 163-166. A solution of 5.5 g (24.4 mmol) of N-trifluoroacetyl-L-glutamic anhydride and 2.6 g (21.8 mmol) of 2-cyano-5-aminopyridine (prepared according to tetrahydrofuran (20 cm3) is stirred for 12 h at 40° C. The solvent is then removed and the residue is dissolved in a 1% solution of sodium carbonate (80 cm3). The solution is rapidly washed with methylene chloride (3×30 cm3) and then acidified to pH 2-3 with a 6 N solution of HCl. Extraction with a solution of ethyl acetate (3×50 cm3), followed by drying over sodium sulfate and then evaporation of the solvent, gives 5.1 g of a crude product, N-trifluoroacetyl-alpha-L-glutamyl-5-aminopyridine-2-carbonitrile, which is obtained pure (melting point: 157° C.) after recrystallization several times from an ethanol/hexane mixture (40/60). After treatment of this compound with a 7.5% solution of ammonia for 4 h at 20° C., followed by concentration to dryness, alpha-L-glutamyl-5-aminopyridine-2-carbonitrile is finally obtained (quantitative yield, melting point: 152° C.). The solvent is then removed the residue is dissolved in a 1% solution of sodium carbonate (80 cm3) The solution is rapidly washed with methylene chloride (3×30 cm3) Extraction with a solution of ethyl acetate (3×50 cm3) by drying over sodium sulfate evaporation of the solvent

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Alpha-L-glutamyl-5-aminopyridine-2-carbonitrile is prepared by the method described in J. Med. Chem., 1973, 16, 163-166. A solution of 5.5 g (24.4 mmol) of N-trifluoroacetyl-L-glutamic anhydride and 2.6 g (21.8 mmol) of 2-cyano-5-aminopyridine (prepared according to tetrahydrofuran (20 cm3) is stirred for 12 h at 40° C. The solvent is then removed and the residue is dissolved in a 1% solution of sodium carbonate (80 cm3). The solution is rapidly washed with methylene chloride (3×30 cm3) and then acidified to pH 2-3 with a 6 N solution of HCl. Extraction with a solution of ethyl acetate (3×50 cm3), followed by drying over sodium sulfate and then evaporation of the solvent, gives 5.1 g of a crude product, N-trifluoroacetyl-alpha-L-glutamyl-5-aminopyridine-2-carbonitrile, which is obtained pure (melting point: 157° C.) after recrystallization several times from an ethanol/hexane mixture (40/60). After treatment of this compound with a 7.5% solution of ammonia for 4 h at 20° C., followed by concentration to dryness, alpha-L-glutamyl-5-aminopyridine-2-carbonitrile is finally obtained (quantitative yield, melting point: 152° C.). The solvent is then removed the residue is dissolved in a 1% solution of sodium carbonate (80 cm3) The solution is rapidly washed with methylene chloride (3×30 cm3) Extraction with a solution of ethyl acetate (3×50 cm3) by drying over sodium sulfate evaporation of the solvent

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

Procedure: Heat at reflux for 3 hours a mixture of N-trifluoroacetyl-L-glutamic anhydride (18.0 g, 80 mmol) and AlCl3 (23.5 g, 177 mmol) in dry benzene (400 ml). Allow to cool, treat with ice (400 ml), conc. HCl (100 ml), and ethyl acetate (EtOAc) (400 ml). Dry the organic layer and concentrate to obtain the title compound as a brown crystalline solid (25 g). Heat at reflux for 3 hours Allow to cool Dry the organic layer concentrate

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

Procedure: Heat at reflux for 3 hours a mixture of N-trifluoroacetyl-L-glutamic anhydride (18.0 g, 80 mmol) and AlCl3 (23.5 g, 177 mmol) in dry benzene (400 ml). Allow to cool, treat with ice (400 ml), conc. HCl (100 ml), and ethylacetate (EtOAc) (400 ml). Dry the organic layer and concentrate to obtain the title compound as a brown crystalline solid (25 g). Heat at reflux for 3 hours Allow to cool Dry the organic layer concentrate

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

Procedure: Heat at reflux for 3 hours a mixture of N-trifluoroacetyl-L-glutamic anhydride (18.0 g, 80 mmol) and AlCl3 (23.5 g, 177 mmol) in dry benzene (400 ml). Allow to cool, treat with ice (400 ml), conc. HCl (100 ml), and ethyl acetate (EtOAc) (400 ml). Dry the organic layer and concentrate to obtain the title compound as a brown crystalline solid (25 g). Heat at reflux for 3 hours Allow to cool Dry the organic layer concentrate

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

Procedure: Heat at reflux for 3 hours a mixture of N-trifluoroacetyl-L-glutamic anhydride (18.0 g, 80 mmol) and AlCl3 (23.5 g, 177 mmol) in dry benzene (400 ml). Allow to cool, treat with ice (400 ml), conc. HCl (100 ml), and ethyl acetate (EtOAc) (400 ml). Dry the organic layer and concentrate to obtain the title compound as a brown crystalline solid (25 g). Heat at reflux for 3 hours Allow to cool Dry the organic layer concentrate

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Alpha-L-glutamyl-5-aminopyridine-2-carbonitrile is prepared by the method described in J. Med. Chem., 1973, 16, 163-166. A solution of 5.5 g (24.4 mmol) of N-trifluoroacetyl-L-glutamic anhydride and 2.6 g (21.8 mmol) of 2-cyano-5-aminopyridine (prepared according to tetrahydrofuran (20 cm3) is stirred for 12 h at 40° C. The solvent is then removed and the residue is dissolved in a 1% solution of sodium carbonate (80 cm3). The solution is rapidly washed with methylene chloride (3×30 cm3) and then acidified to pH 2-3 with a 6 N solution of HCl. Extraction with a solution of ethyl acetate (3×50 cm3), followed by drying over sodium sulfate and then evaporation of the solvent, gives 5.1 g of a crude product, N-trifluoroacetyl-alpha-L-glutamyl-5-aminopyridine-2-carbonitrile, which is obtained pure (melting point: 157° C.) after recrystallization several times from an ethanol/hexane mixture (40/60). After treatment of this compound with a 7.5% solution of ammonia for 4 h at 20° C., followed by concentration to dryness, alpha-L-glutamyl-5-aminopyridine-2-carbonitrile is finally obtained (quantitative yield, melting point: 152° C.). The solvent is then removed the residue is dissolved in a 1% solution of sodium carbonate (80 cm3) The solution is rapidly washed with methylene chloride (3×30 cm3) Extraction with a solution of ethyl acetate (3×50 cm3) by drying over sodium sulfate evaporation of the solvent