3-(aminomethyl)-N,N-dimethylaniline

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A mixture of 7-amino-4-methylthiopyrido[4,3-d]pyrimidine (236 mg, 1.23 mmol) (described in a previous experimental) and 3-dimethylamino-benzylamine (1.36 g, 9.07 mmol) in isopropanol (5 mL) is stirred under N2 at reflux for 1 h, and the resulting product is chromatographed on silica gel (10-15% EtOH/EtOAc), then on alumina (1% EtOH/CHCl3) to give 7-amino-4-(3-dimethylaminobenzylamino)pyrido[4,3-d]pyrimidine (145 mg, 40%) as a white solid. 1H NMR (DMSO) δ 9.11 (1H, s), 8.79 (1H, t, J=5.9 Hz), 8.26 (1H, s), 7.11 (1H, dd, J=8.0, 7.7 Hz), 6.73 (1H, brs), 6.63 (1H, d, J=7.6 Hz), 6.60 (1H, dd, J=8.1, 2.2 Hz), 6.44 (2H, brs), 6.35 (1H, S), 4.67 (2H, d, J=5.8 Hz), 2.86 (6H, s). at reflux for 1 h the resulting product is chromatographed on silica gel (10-15% EtOH/EtOAc)

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

実験手順: Following the procedure as describe in Example 16, making variations as required to replace 2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid with 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxylic acid to react with 3-(aminomethyl)-N,N-dimethylaniline, the title compound was obtained as a colourless solid in 50% yield: mp 149-151° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.78 (t, J=5.9 Hz, 1H), 8.71 (s, 1H), 7.35 (dd, J=8.5, 5.6 Hz, 1H), 7.15 (d, J=8.9 Hz, 1H), 7.09 (dd, J=7.9, 6.9 Hz, 2H), 6.66 (s, 1H), 6.58 (dd, J=7.7, 7.7 Hz, 2H), 4.96 (s, 2H), 4.35 (d, J=5.8 Hz, 2H), 2.83 (s, 6H); 13C NMR (75 MHz, DMSO-d6) δ163.7, 161.3, 160.5, 151.6, 151.2, 150.9, 150.1, 140.3, 132.7 (d, 3JC-F=11 Hz), 132.4, 130.4 (d, 2JC-F=33 Hz), 129.2, 123.1, 115.9 (d, 1JC-F=86 Hz), 115.6, 111.7, 111.4, 48.2, 43.6, 40.5, 17.3; MS (ES+) m/z 467.16 (M+1).

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

実験手順: Following the procedure as describe in Example 16, making variations as required to replace 2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid with 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxylic acid to react with 3-(aminomethyl)-N,N-dimethylaniline, the title compound was obtained as a colourless solid in 50% yield: mp 149-151° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.78 (t, J=5.9 Hz, 1H), 8.71 (s, 1H), 7.35 (dd, J=8.5, 5.6 Hz, 1H), 7.15 (d, J=8.9 Hz, 1H), 7.09 (dd, J=7.9, 6.9 Hz, 2H), 6.66 (s, 1H), 6.58 (dd, J=7.7, 7.7 Hz, 2H), 4.96 (s, 2H), 4.35 (d, J=5.8 Hz, 2H), 2.83 (s, 6H); 13C NMR (75 MHz, DMSO-d6) δ163.7, 161.3, 160.5, 151.6, 151.2, 150.9, 150.1, 140.3, 132.7 (d, 3JC-F=11 Hz), 132.4, 130.4 (d, 2JC-F=33 Hz), 129.2, 123.1, 115.9 (d, 1JC-F=86 Hz), 115.6, 111.7, 111.4, 48.2, 43.6, 40.5, 17.3; MS (ES+) m/z 467.16 (M+1).

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

実験手順: 2′-Methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxylic acid (11.3 mg, 0.034 mmol), HOBT (6.0 mg, 0.044 mmol), 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (8.0 mg, 0.042 mmol) and 3-dimethylaminobenzylamine (0.34 mmol) were mixed in DMF (0.7 ml) and the reaction left at room temperature for 18 h. The DMF was evaporated under vacuum and the residue partitioned between DCM (0.4 ml) and water (0.4 ml). The organic phase was washed with aqueous sodium hydroxide (0.5M, 0.2 ml) and the DCM evaporated under vacuum. The residue was purified by mass directed HPLC to give N-(3-dimethylaminobenzyl)-2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxamide. LCMS; retention time 3.11 min, MH+ 427. The DMF was evaporated under vacuum the residue partitioned between DCM (0.4 ml) and water (0.4 ml) The organic phase was washed with aqueous sodium hydroxide (0.5M, 0.2 ml) the DCM evaporated under vacuum The residue was purified by mass

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

実験手順: A mixture of 7-amino-4-methylthiopyrido[4,3-d]pyrimidine (236 mg, 1.23 mmol) (described in a previous experimental) and 3-dimethylamino-benzylamine (1.36 g, 9.07 mmol) in isopropanol (5 mL) is stirred under N2 at reflux for 1 h, and the resulting product is chromatographed on silica gel (10-15% EtOH/EtOAc), then on alumina (1% EtOH/CHCl3) to give 7-amino-4-(3-dimethylaminobenzylamino)pyrido[4,3-d]pyrimidine (145 mg, 40%) as a white solid. 1H NMR (DMSO) δ 9.11 (1H, s), 8.79 (1H, t, J=5.9 Hz), 8.26 (1H, s), 7.11 (1H, dd, J=8.0, 7.7 Hz), 6.73 (1H, brs), 6.63 (1H, d, J=7.6 Hz), 6.60 (1H, dd, J=8.1, 2.2 Hz), 6.44 (2H, brs), 6.35 (1H, s), 4.67 (2H, d, J=5.8 Hz), 2.86 (6H, s). at reflux for 1 h the resulting product is chromatographed on silica gel (10-15% EtOH/EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 2′-Methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxylic acid (11.3 mg, 0.034 mmol), HOBT (6.0 mg, 0.044 mmol), 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (8.0 mg, 0.042 mmol) and 3-dimethylaminobenzylamine (0.34 mmol) were mixed in DMF (0.7 ml) and the reaction left at room temperature for 18 h. The DMF was evaporated under vacuum and the residue partitioned between DCM (0.4 ml) and water (0.4 ml). The organic phase was washed with aqueous sodium hydroxide (0.5M, 0.2 ml) and the DCM evaporated under vacuum. The residue was purified by mass directed HPLC to give N-(3-dimethylaminobenzyl)-2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxamide. LCMS; retention time 3.11 min, MH+ 427. The DMF was evaporated under vacuum the residue partitioned between DCM (0.4 ml) and water (0.4 ml) The organic phase was washed with aqueous sodium hydroxide (0.5M, 0.2 ml) the DCM evaporated under vacuum The residue was purified by mass