(S)-N-Phenyl-2-pyrrolidinecarboxamide

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

実験手順: To 45 ml of an ethyl acetate solution of Nα -benzyloxycarbonyl-L-histidine azide (4) prepared from 3.03 g of Nα -benzyloxycarbonyl-L-histidine hydrazide (3) by a known method was added 1.52 g of compound (94) under ice-cooling and the reaction was maintained overnight in a refrigerator. The reaction mixture was concentrated and the residue thus formed was subjected to silica gel column chromatography. By eluting the product with chloroform-methanol (95:5), 2.49 g of Nα -benzyloxycarbonyl-L-histidyl-N-phenyl-L-prolinamide (95) was obtained. cooling the reaction was maintained overnight in a refrigerator The reaction mixture was concentrated the residue thus formed By eluting the product with chloroform-methanol (95:5)

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

実験手順: To 45 ml of an ethyl acetate solution of Nα -benzyloxycarbonyl-L-histidine azide (4) prepared from 3.03 g of Nα -benzyloxycarbonyl-L-histidine hydrazide (3) by a known method was added 1.52 g of compound (94) under ice-cooling and the reaction was maintained overnight in a refrigerator. The reaction mixture was concentrated and the residue thus formed was subjected to silica gel column chromatography. By eluting the product with chloroform-methanol (95:5), 2.49 g of Nα -benzyloxycarbonyl-L-histidyl-N-phenyl-L-prolinamide (95) was obtained. cooling the reaction was maintained overnight in a refrigerator The reaction mixture was concentrated the residue thus formed By eluting the product with chloroform-methanol (95:5)

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

実験手順: In 150 ml of methanol was dissolved 4.87 g of compound (93) and the compound was hydrogenated using 487 mg of 10% palladium-carbon as a catalyst. The catalyst was filtered off and the filtrate was concentrated to provide 2.79 g of (S)-N-phenyl-2-pyrrolidinecarboxamide (94). The catalyst was filtered off the filtrate was concentrated

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

実験手順: To 45 ml of an ethyl acetate solution of Nα -benzyloxycarbonyl-L-histidine azide (4) prepared from 3.03 g of Nα -benzyloxycarbonyl-L-histidine hydrazide (3) by a known method was added 1.52 g of compound (94) under ice-cooling and the reaction was maintained overnight in a refrigerator. The reaction mixture was concentrated and the residue thus formed was subjected to silica gel column chromatography. By eluting the product with chloroform-methanol (95:5), 2.49 g of Nα -benzyloxycarbonyl-L-histidyl-N-phenyl-L-prolinamide (95) was obtained. cooling the reaction was maintained overnight in a refrigerator The reaction mixture was concentrated the residue thus formed By eluting the product with chloroform-methanol (95:5)

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

実験手順: In 150 ml of methanol was dissolved 4.87 g of compound (93) and the compound was hydrogenated using 487 mg of 10% palladium-carbon as a catalyst. The catalyst was filtered off and the filtrate was concentrated to provide 2.79 g of (S)-N-phenyl-2-pyrrolidinecarboxamide (94). The catalyst was filtered off the filtrate was concentrated

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

実験手順: To 45 ml of an ethyl acetate solution of Nα -benzyloxycarbonyl-L-histidine azide (4) prepared from 3.03 g of Nα -benzyloxycarbonyl-L-histidine hydrazide (3) by a known method was added 1.52 g of compound (94) under ice-cooling and the reaction was maintained overnight in a refrigerator. The reaction mixture was concentrated and the residue thus formed was subjected to silica gel column chromatography. By eluting the product with chloroform-methanol (95:5), 2.49 g of Nα -benzyloxycarbonyl-L-histidyl-N-phenyl-L-prolinamide (95) was obtained. cooling the reaction was maintained overnight in a refrigerator The reaction mixture was concentrated the residue thus formed By eluting the product with chloroform-methanol (95:5)

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

実験手順: In 150 ml of methanol was dissolved 4.87 g of compound (93) and the compound was hydrogenated using 487 mg of 10% palladium-carbon as a catalyst. The catalyst was filtered off and the filtrate was concentrated to provide 2.79 g of (S)-N-phenyl-2-pyrrolidinecarboxamide (94). The catalyst was filtered off the filtrate was concentrated

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

実験手順: To a solution of (S)-(+)-N-Boc-2-phenylaminocarbonylpyrrolidine (1.1 g, 3.8 mmol) in 5 mL of CH2Cl2 at 0° C. was added 5 mL of TFA dropwise over 1 hour. The solution was warmed to room temperature and stirred for 1.5 hours. To the reaction mixture was added 100 mL of water and the aqueous layer was washed with EtOAc. The aqueous layer was then made basic with 30 mL of 10% NaOH and extracted therein with 20 mL EtOAc. The organic layer was then dried over Na2SO4, filtered and concentrated under reduced pressure to give a white solid (0.40 g, 56%). ES (+) MS m/e=191 (M+H). the aqueous layer was washed with EtOAc extracted The organic layer was then dried over Na2SO4 filtered concentrated under reduced pressure

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

実験手順: To 45 ml of an ethyl acetate solution of Nα -benzyloxycarbonyl-L-histidine azide (4) prepared from 3.03 g of Nα -benzyloxycarbonyl-L-histidine hydrazide (3) by a known method was added 1.52 g of compound (94) under ice-cooling and the reaction was maintained overnight in a refrigerator. The reaction mixture was concentrated and the residue thus formed was subjected to silica gel column chromatography. By eluting the product with chloroform-methanol (95:5), 2.49 g of Nα -benzyloxycarbonyl-L-histidyl-N-phenyl-L-prolinamide (95) was obtained. cooling the reaction was maintained overnight in a refrigerator The reaction mixture was concentrated the residue thus formed By eluting the product with chloroform-methanol (95:5)

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

実験手順: In 150 ml of methanol was dissolved 4.87 g of compound (93) and the compound was hydrogenated using 487 mg of 10% palladium-carbon as a catalyst. The catalyst was filtered off and the filtrate was concentrated to provide 2.79 g of (S)-N-phenyl-2-pyrrolidinecarboxamide (94). The catalyst was filtered off the filtrate was concentrated

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

実験手順: 201 mg (1.05 mmol) of EDCl was added to 5 ml of THF solution of 100 mg (0.526 mmol) of Boc-Pro-OH (manufactured by Tokyo Chemical Industry Co., Ltd), and 113 mg (0.526 mmol) of H-Pro-NHPh (manufactured by Tokyo Chemical Industry Co., Ltd), followed by stirring for 6 hours at room temperature. After a reaction mixture was concentrated under reduced pressure, the concentrate was extracted by adding water and ethyl acetate. After an organic layer was washed sequentially with a diluted hydrochloric acid, an aqueous solution of sodium hydrogen carbonate and water (one time for each), it was concentrated under reduced pressure, thereby obtaining crude amide. The obtained amide compound was purified by a silica gel column chromatography (hexane/ethyl acetate=5/1 to 1/1 (volume ratio)), thereby obtaining 150 mg of the product with a yield of 73.6%. After a reaction mixture was concentrated under reduced pressure the concentrate was extracted by adding water and ethyl acetate After an organic layer was washed sequentially with a diluted hydrochloric acid an aqueous solution of sodium hydrogen carbonate and water (one time for each), it was concentrated under reduced pressure obtaining crude amide The obtained amide compound was purified by a silica gel column chromatography (hexane/ethyl acetate=5/1 to 1/1 (volume ratio))

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

実験手順: To 45 ml of an ethyl acetate solution of Nα -benzyloxycarbonyl-L-histidine azide (4) prepared from 3.03 g of Nα -benzyloxycarbonyl-L-histidine hydrazide (3) by a known method was added 1.52 g of compound (94) under ice-cooling and the reaction was maintained overnight in a refrigerator. The reaction mixture was concentrated and the residue thus formed was subjected to silica gel column chromatography. By eluting the product with chloroform-methanol (95:5), 2.49 g of Nα -benzyloxycarbonyl-L-histidyl-N-phenyl-L-prolinamide (95) was obtained. cooling the reaction was maintained overnight in a refrigerator The reaction mixture was concentrated the residue thus formed By eluting the product with chloroform-methanol (95:5)