5-bromo-2-cyclopropylisoindolin-1-oneCAS Registry Number 864866-56-8 Name: 1H-Isoindol-1-one, 5-bromo-2-cyclopropyl-2,3-dihydro- 5-Bromo-2-cyclopropylisoindolin-1-one

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of potassium carbonate (0.10 g, 0.75 mmol) in water (0.7 mL) was added to a mixture of 5-bromo-2-cyclopropylisoindolin-1-one (0.095 g, 0.38 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (0.12 g, 0.56 mmol), and tetrakis(triphenylphosphine)palladium (0.02 g, 0.02 mmol) in toluene (1.4 mL) and ethanol (0.7 mL). The resulting mixture was heated at 120° C. for 15 min. The reaction mixture was then quenched with saturated sodium bicarbonate (5 mL) and extracted with EtOAc. The organic layers were washed with brine, dried with anhydrous Na2SO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with 10% methanol in dichloromethane to afford the desired product (0.046 g, 46%). LCMS: (M+H)=267.1. The reaction mixture was then quenched with saturated sodium bicarbonate (5 mL) extracted with EtOAc The organic layers were washed with brine dried with anhydrous Na2SO4 filtered concentrated The residue was purified by chromatography on silica gel with 10% methanol in dichloromethane

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 4-bromo-2-(bromomethyl)benzoate (0.13 g, 0.42 mmol), cyclopropylamine (0.034 mL, 0.49 mmol) and potassium carbonate (0.090 g, 0.65 mmol) in ethanol (0.9 mL) was stirred at 40° C. for 3 h. The reaction mixture was quenched with saturated sodium bicarbonate and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes to afford the desired product (0.10 g, 94%). LCMS: (M+H)=252.0/254.0. The reaction mixture was quenched with saturated sodium bicarbonate extracted with EtOAc (3×20 mL) The combined organic layers were washed with brine dried over anhydrous Na2SO4 filtered concentrated The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 4-bromo-2-(bromomethyl)benzoate (0.13 g, 0.42 mmol), cyclopropylamine (0.034 mL, 0.49 mmol) and potassium carbonate (0.090 g, 0.65 mmol) in ethanol (0.9 mL) was stirred at 40° C. for 3 h. The reaction mixture was quenched with saturated sodium bicarbonate and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes to afford the desired product (0.10 g, 94%). LCMS: (M+H)=252.0/254.0. The reaction mixture was quenched with saturated sodium bicarbonate extracted with EtOAc (3×20 mL) The combined organic layers were washed with brine dried over anhydrous Na2SO4 filtered concentrated The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 4-bromo-2-(bromomethyl)benzoate (0.13 g, 0.42 mmol), cyclopropylamine (0.034 mL, 0.49 mmol) and potassium carbonate (0.090 g, 0.65 mmol) in ethanol (0.9 mL) was stirred at 40° C. for 3 h. The reaction mixture was quenched with saturated sodium bicarbonate and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes to afford the desired product (0.10 g, 94%). LCMS (M+H)+: m/z=252.0/254.0. The reaction mixture was quenched with saturated sodium bicarbonate extracted with EtOAc (3×20 mL) The combined organic layers were washed with brine dried over anhydrous Na2SO4 filtered concentrated The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes

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

实验步骤: Methyl 4-bromo-2-(bromomethyl)benzoate (1A2) (1.62 mmol, 500 mg) and cyclopropylamine (1A3) (3.25 mmol, 185 mg) in methanol (3 ml) were heated in the microwave at 120° C. for 10 mins. The reaction mixture was concentrated and purified on silica eluting with 50-100% EtOAc/heptane to yield 5-bromo-2-cyclopropylisoindolin-1-one (1A4) 350 mg (84%); 1H NMR (400 MHz, CDCl3) δ 7.96 (d, 1H) 7.59 (d, 1H) 7.78 (s, 1H) 4.30 (s, 2H) 2.91 (m, 1H) 0.94-0.85 (m, 4H). The reaction mixture was concentrated purified on silica eluting with 50-100% EtOAc/heptane

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

实验步骤: A mixture of methyl 4-bromo-2-(bromomethyl)benzoate (Ark Pharm, Cat. No. AK-26333) (0.5 g, 0.002 mol), cyclopropylamine (0.17 mL, 0.0024 mol) and potassium carbonate (0.45 g, 0.0032 mol) in ethanol (5 mL) was stirred at 40° C. for 3 h. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layers were washed with brine, dried with Na2SO4, filtered, and concentrated under reduced pressure to give a crude product which was directly used in nest step reaction without further purification. LCMS (M+H)+=252.0/254.0. The reaction mixture was quenched with water extracted with ethyl acetate The organic layers were washed with brine dried with Na2SO4 filtered concentrated under reduced pressure

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of potassium carbonate (0.10 g, 0.75 mmol) in water (0.7 mL) was added to a mixture of 5-bromo-2-cyclopropylisoindolin-1-one (0.095 g, 0.38 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (0.12 g, 0.56 mmol), and tetrakis(triphenylphosphine)palladium (0.02 g, 0.02 mmol) in toluene (1.4 mL) and ethanol (0.7 mL). The resulting mixture was heated at 120° C. for 15 min. The reaction mixture was then quenched with saturated sodium bicarbonate (5 mL) and extracted with EtOAc. The organic layers were washed with brine, dried with anhydrous Na2SO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with 10% methanol in dichloromethane to afford the desired product (0.046 g, 46%). LCMS: (M+H)=267.1. The reaction mixture was then quenched with saturated sodium bicarbonate (5 mL) extracted with EtOAc The organic layers were washed with brine dried with anhydrous Na2SO4 filtered concentrated The residue was purified by chromatography on silica gel with 10% methanol in dichloromethane

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 4-bromo-2-(bromomethyl)benzoate (0.13 g, 0.42 mmol), cyclopropylamine (0.034 mL, 0.49 mmol) and potassium carbonate (0.090 g, 0.65 mmol) in ethanol (0.9 mL) was stirred at 40° C. for 3 h. The reaction mixture was quenched with saturated sodium bicarbonate and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes to afford the desired product (0.10 g, 94%). LCMS: (M+H)=252.0/254.0. The reaction mixture was quenched with saturated sodium bicarbonate extracted with EtOAc (3×20 mL) The combined organic layers were washed with brine dried over anhydrous Na2SO4 filtered concentrated The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of potassium carbonate (0.10 g, 0.75 mmol) in water (0.7 mL) was added to a mixture of 5-bromo-2-cyclopropylisoindolin-1-one (0.095 g, 0.38 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (0.12 g, 0.56 mmol), and tetrakis(triphenylphosphine)palladium (0.02 g, 0.02 mmol) in toluene (1.4 mL) and ethanol (0.7 mL). The resulting mixture was heated at 120° C. for 15 min. The reaction mixture was then quenched with saturated sodium bicarbonate (5 mL) and extracted with EtOAc. The organic layers were washed with brine, dried with anhydrous Na2SO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with 10% methanol in dichloromethane to afford the desired product (0.046 g, 46%). LCMS: (M+H)=267.1. The reaction mixture was then quenched with saturated sodium bicarbonate (5 mL) extracted with EtOAc The organic layers were washed with brine dried with anhydrous Na2SO4 filtered concentrated The residue was purified by chromatography on silica gel with 10% methanol in dichloromethane

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 4-bromo-2-(bromomethyl)benzoate (0.13 g, 0.42 mmol), cyclopropylamine (0.034 mL, 0.49 mmol) and potassium carbonate (0.090 g, 0.65 mmol) in ethanol (0.9 mL) was stirred at 40° C. for 3 h. The reaction mixture was quenched with saturated sodium bicarbonate and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes to afford the desired product (0.10 g, 94%). LCMS: (M+H)=252.0/254.0. The reaction mixture was quenched with saturated sodium bicarbonate extracted with EtOAc (3×20 mL) The combined organic layers were washed with brine dried over anhydrous Na2SO4 filtered concentrated The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes