巴瑞替尼杂质18

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:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: To a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.40 g, 2.0 mmol, Aldrich, Cat. 525057) and tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (0.40 g, 2.0 mmol) in acetonitrile (7 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.37 mL, 2.5 mmol). The mixture was stirred at 70° C. overnight. The mixture was concentrated. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-90%) to afford the desired product. LCMS (M+Na)+: m/z=411.2. The mixture was concentrated The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-90%)

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:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.06 g, 5.10 mmol), tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (1.00 g, 5.15 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.38 mL, 2.6 mmol) in acetonitrile (20 mL) was heated at 60° C. for 2 h. After cooling, the solvent was removed under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexanes (0-60%) to afford the desired product. LCMS cacld. for C16H24BN4O4 (M−55)+: m/z=347.2. Found: 347.1. After cooling the solvent was removed under reduced pressure The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexanes (0-60%)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.06 g, 5.10 mmol), tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (1.00 g, 5.15 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.38 mL, 2.6 mmol) in acetonitrile (20 mL) was heated at 60° C. for 2 h. After cooling, the solvent was removed under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexanes (0-60%) to afford the desired product. LCMS cacld. for C16H24BN4O4 (M−55)+: m/z=347.2. Found: 347.1. After cooling the solvent was removed under reduced pressure The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexanes (0-60%)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.990 g, 5.10 mmol), tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (1.00 g, 5.15 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.38 mL, 2.6 mmol) in acetonitrile (20 mL) was heated at 60° C. for 2 h. After cooling, the solvent was removed under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexanes (0-60%) to afford the desired product (1.68 g, 84.8%). LCMS cacld. for C15H22BN4O4 (M−55)+: m/z=333.2. Found: 333.1. After cooling the solvent was removed under reduced pressure The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexanes (0-60%)