(S)-4-(1-AMINOMETHYL)PYRROLIDINE-2-ONE

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

实验步骤: 224 mg (R)-4-Hydroxymethyl-pyrrolidine-2-one (2.2) was placed in 1.5 mL of dimethylacetamide at ambient temperature under nitrogen. The reaction was stirred for 10 min before 5-chloro-7-(3-fluoro-4-isopropoxy-phenyl)-[1,6]naphthyridine (6.41) as a solution in 3 mL dimethylacetamide was introduced. The reaction was heated to 100° C. for 3 h and then cooled to ambient temperature. Water was added and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 90:10) gave the title compound. was introduced cooled to ambient temperature the mixture was extracted with ethyl acetate (×3) The combined organic fractions were dried over sodium sulfate filtered the filtrate was concentrated under reduced pressure Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 90:10)

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

实验步骤: 91 mg (R)-4-Hydroxymethyl-pyrrolidine-2-one (2.2) was placed in 1 mL of dimethylacetamide at ambient temperature under nitrogen. The reaction was stirred for 10 min before 210 mg 5-chloro-7-[3-methoxy-4-(tetrahydro-pyran-4-yloxy)-phenyl]-[1,6]naphthyridine (6.36) as a solution in 1.5 mL dimethylacetamide was introduced. The reaction was stirred overnight at ambient temperature and then heated to 70° C. where it was maintained for 2 h. After this time the mixture was cooled to ambient temperature and it was partitioned between water and ethyl acetate. The aqueous layer was separated and it was extracted with additional ethyl acetate (×2). The combined organic fractions were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 92:8) gave the title compound. was introduced heated to 70° C. where it was maintained for 2 h After this time the mixture was cooled to ambient temperature it was partitioned between water and ethyl acetate The aqueous layer was separated it was extracted with additional ethyl acetate (×2) The combined organic fractions were dried over sodium sulfate filtered the filtrate was concentrated under reduced pressure Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 92:8)

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 100 mg 6.1 and 30 mg of (S)-4-(aminomethyl)pyrrolidin-2-one (2.2) were dissolved in dimethylacetamide. 0.175 mL of diisopropylethylamine was added and the mixture was heated at 70° C. overnight. The mixture was diluted with water and methanol and purified via chromatography (RP-HPLC) and the corresponding fractions were freeze-dried. purified via chromatography (RP-HPLC) the corresponding fractions were freeze-dried

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 100 mg 6.1 and 30 mg of (S)-4-(aminomethyl)pyrrolidin-2-one (2.2) were dissolved in dimethylacetamide. 0.175 mL of diisopropylethylamine was added and the mixture was heated at 70° C. overnight. The mixture was diluted with water and methanol and purified via chromatography (RP-HPLC) and the corresponding fractions were freeze-dried. purified via chromatography (RP-HPLC) the corresponding fractions were freeze-dried

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

实验步骤: 224 mg (R)-4-Hydroxymethyl-pyrrolidine-2-one (2.2) was placed in 1.5 mL of dimethylacetamide at ambient temperature under nitrogen. The reaction was stirred for 10 min before 5-chloro-7-(3-fluoro-4-isopropoxy-phenyl)-[1,6]-naphthyridine (6.41) as a solution in 3 mL dimethylacetamide was introduced. The reaction was heated to 100° C. for 3 h and then cooled to ambient temperature. Water was added and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 90:10) gave the title compound. was introduced cooled to ambient temperature the mixture was extracted with ethyl acetate (×3) The combined organic fractions were dried over sodium sulfate filtered the filtrate was concentrated under reduced pressure Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 90:10)

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

实验步骤: 91 mg (R)-4-Hydroxymethyl-pyrrolidine-2-one (2.2) was placed in 1 mL of dimethylacetamide at ambient temperature under nitrogen. The reaction was stirred for 10 min before 210 mg 5-chloro-7-[3-methoxy-4-(tetrahydro-pyran-4-yloxy)-phenyl]-[1,6]naphthyridine (6.36) as a solution in 1.5 mL dimethylacetamide was introduced. The reaction was stirred overnight at ambient temperature and then heated to 70° C. where it was maintained for 2 h. After this time the mixture was cooled to ambient temperature and it was partitioned between water and ethyl acetate. The aqueous layer was separated and it was extracted with additional ethyl acetate (×2). The combined organic fractions were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 92:8) gave the title compound. was introduced heated to 70° C. where it was maintained for 2 h After this time the mixture was cooled to ambient temperature it was partitioned between water and ethyl acetate The aqueous layer was separated it was extracted with additional ethyl acetate (×2) The combined organic fractions were dried over sodium sulfate filtered the filtrate was concentrated under reduced pressure Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 92:8)

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

实验步骤: 91 mg (R)-4-Hydroxymethyl-pyrrolidine-2-one (2.2) was placed in 1 mL of dimethylacetamide at ambient temperature under nitrogen. The reaction was stirred for 10 min before 210 mg 5-chloro-7-[3-methoxy-4-(tetrahydro-pyran-4-yloxy)-phenyl]-[1,6]naphthyridine (6.36) as a solution in 1.5 mL dimethylacetamide was introduced. The reaction was stirred overnight at ambient temperature and then heated to 70° C. where it was maintained for 2 h. After this time the mixture was cooled to ambient temperature and it was partitioned between water and ethyl acetate. The aqueous layer was separated and it was extracted with additional ethyl acetate (×2). The combined organic fractions were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 92:8) gave the title compound. was introduced heated to 70° C. where it was maintained for 2 h After this time the mixture was cooled to ambient temperature it was partitioned between water and ethyl acetate The aqueous layer was separated it was extracted with additional ethyl acetate (×2) The combined organic fractions were dried over sodium sulfate filtered the filtrate was concentrated under reduced pressure Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 92:8)

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 100 mg 6.1 and 30 mg of (S)-4-(aminomethyl)pyrrolidin-2-one (2.2) were dissolved in dimethylacetamide. 0.175 mL of diisopropylethylamine was added and the mixture was heated at 70° C. overnight. The mixture was diluted with water and methanol and purified via chromatography (RP-HPLC) and the corresponding fractions were freeze-dried. purified via chromatography (RP-HPLC) the corresponding fractions were freeze-dried

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

实验步骤: 224 mg (R)-4-Hydroxymethyl-pyrrolidine-2-one (2.2) was placed in 1.5 mL of dimethylacetamide at ambient temperature under nitrogen. The reaction was stirred for 10 min before 5-chloro-7-(3-fluoro-4-isopropoxy-phenyl)-[1,6]naphthyridine (6.41) as a solution in 3 mL dimethylacetamide was introduced. The reaction was heated to 100° C. for 3 h and then cooled to ambient temperature. Water was added and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 90:10) gave the title compound. was introduced cooled to ambient temperature the mixture was extracted with ethyl acetate (×3) The combined organic fractions were dried over sodium sulfate filtered the filtrate was concentrated under reduced pressure Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 90:10)

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

实验步骤: 91 mg (R)-4-Hydroxymethyl-pyrrolidine-2-one (2.2) was placed in 1 mL of dimethylacetamide at ambient temperature under nitrogen. The reaction was stirred for 10 min before 210 mg 5-chloro-7-[3-methoxy-4-(tetrahydro-pyran-4-yloxy)-phenyl]-[1,6]naphthyridine (6.36) as a solution in 1.5 mL dimethylacetamide was introduced. The reaction was stirred overnight at ambient temperature and then heated to 70° C. where it was maintained for 2 h. After this time the mixture was cooled to ambient temperature and it was partitioned between water and ethyl acetate. The aqueous layer was separated and it was extracted with additional ethyl acetate (×2). The combined organic fractions were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 92:8) gave the title compound. was introduced heated to 70° C. where it was maintained for 2 h After this time the mixture was cooled to ambient temperature it was partitioned between water and ethyl acetate The aqueous layer was separated it was extracted with additional ethyl acetate (×2) The combined organic fractions were dried over sodium sulfate filtered the filtrate was concentrated under reduced pressure Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 92:8)

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 100 mg 6.1 and 30 mg of (S)-4-(aminomethyl)pyrrolidin-2-one (2.2) were dissolved in dimethylacetamide. 0.175 mL of diisopropylethylamine was added and the mixture was heated at 70° C. overnight. The mixture was diluted with water and methanol and purified via chromatography (RP-HPLC) and the corresponding fractions were freeze-dried. purified via chromatography (RP-HPLC) the corresponding fractions were freeze-dried

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

实验步骤: 224 mg (R)-4-Hydroxymethyl-pyrrolidine-2-one (2.2) was placed in 1.5 mL of dimethylacetamide at ambient temperature under nitrogen. The reaction was stirred for 10 min before 5-chloro-7-(3-fluoro-4-isopropoxy-phenyl)-[1,6]-naphthyridine (6.41) as a solution in 3 mL dimethylacetamide was introduced. The reaction was heated to 100° C. for 3 h and then cooled to ambient temperature. Water was added and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 90:10) gave the title compound. was introduced cooled to ambient temperature the mixture was extracted with ethyl acetate (×3) The combined organic fractions were dried over sodium sulfate filtered the filtrate was concentrated under reduced pressure Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 90:10)