美利曲辛杂质4

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: A solution of 2.4 ml of acetic anhydride in 10 ml of tetrahydrofuran is added dropwise to a solution of 4 g of 1-(4-aminophenyl)-3-azabicyclo[3.1.0]hexane-2,4-dione and 120 mg of dimethylaminopropane in 150 ml of tetradrofuran, and the mixture is stirred overnight at room temperature. Then 0.5 ml of ethanol is added to the reaction mixture, which is stirred for 1 hour and filtered. The crystals so obtained are washed with tetrahydrofuran and ether, affording white crystals of the title compound with a melting point above 230° C. and Rf=0.3 in thin-layer silica gel plates in the system methylene chloride/methanol (10:1). is stirred for 1 hour filtered The crystals so obtained are washed with tetrahydrofuran and 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 Example A3 (1.00 g, 2.84 mmol) in DMF (10 mL) was added N,N-dimethylpropaneamine (0.870 g, 8.52 mmol) and the resulting reaction mixture was heated at 100° C. for 36 h. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), and the solvent evaporated to provide 3-(5-amino-2-chloro-4-fluorophenyl)-7-(3-(dimethylamino)propylamino)-1-ethyl-1,6-naphthyridin-2(1H)-one (1.10 g, 93% yield) as an orange foam. 1H NMR (400 MHz, DMSO-d6): δ 8.36 (s, 1H), 7.64 (s, 1H), 7.20 (d, J=11 Hz, 1H), 7.03 (m, 1H), 6.76 (d, J=9 Hz, 1H), 6.27 (s, 1H), 5.30 (s, 2H), 4.08 (m, 2H), 3.30 (m, 2H), 2.26 (t, J=6 Hz, 2H), 2.05 (m, 6H), 1.66 (m, 2H), 1.18 (t, J=6 Hz, 3H); MS (ESI) m/z: 418.2.2 [M+H]+. the resulting reaction mixture extracted with EtOAc (3×) The combined organic layers were washed with brine dried (MgSO4) the solvent evaporated

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

实验步骤: To a solution of Example A3 (1.00 g, 2.84 mmol) in DMF (10 mL) was added N,N-dimethylpropaneamine (0.870 g, 8.52 mmol) and the resulting reaction mixture was heated at 100° C. for 36 h. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), and the solvent evaporated to provide 3-(5-amino-2-chloro-4-fluorophenyl)-7-(3-(dimethylamino)propylamino)-1-ethyl-1,6-naphthyridin-2(1H)-one (1.10 g, 93% yield) as an orange foam. 1H NMR (400 MHz, DMSO-d6): δ 8.36 (s, 1H), 7.64 (s, 1H), 7.20 (d, J=11 Hz, 1H), 7.03 (m, 1H), 6.76 (d, J=9 Hz, 1H), 6.27 (s, 1H), 5.30 (s, 2H), 4.08 (m, 2H), 3.30 (m, 2H), 2.26 (t, J=6 Hz, 2H), 2.05 (m, 6H), 1.66 (m, 2H), 1.18 (t, J=6 Hz, 3H); MS (ESI) m/z: 418.2.2 [M+H]+. the resulting reaction mixture extracted with EtOAc (3×) The combined organic layers were washed with brine dried (MgSO4) the solvent evaporated