乙基2-(环丙基氨基)-2-氧亚基醋酸盐

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

实验步骤: To a mixture of 4-[(3-aminopyridin-2-yl)amino]-2-fluorobenzonitrile (C15) (3.9 g, 17 mmol) and ethyl(cyclopropylamino)(oxo)acetate (P1) (4.03 g, 25.6 mmol) in 1-methylpyrrolidin-2-one (17 mL) was added potassium tert-butoxide (2.88 g, 25.7 mmol). The reaction mixture was stirred at 120° C. for 30 minutes, cooled to room temperature, and treated with 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (T3P) (˜50% weight solution, 20.3 mL, 32 mmol). After the reaction mixture had been stirred at 120° C. for 18 hours, it was allowed to cool. Water (10 mL) was added and stirring was continued for 10 minutes. Saturated aqueous sodium bicarbonate solution (20 mL) was introduced, and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution, filtered, and concentrated in vacuo Silica gel chromatography (Gradient: 10% to 50% ethyl acetate in petroleum ether) afforded the product as a white solid. Yield: 2.29 g, 7.13 mmol, 42%. LCMS m/z 322.2 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.50 (dd, J=4.7, 1.4 Hz, 1H), 8.17 (dd, J=8.2, 1.5 Hz, 1H), 7.79-7.85 (m, 1H), 7.69 (br s, 1H), 7.38-7.45 (m, 3H), 2.83-2.90 (m, 1H), 0.87-0.93 (m, 2H), 0.68-0.73 (m, 2H). cooled to room temperature After the reaction mixture had been stirred at 120° C. for 18 hours to cool stirring was continued for 10 minutes the mixture was extracted with ethyl acetate (3×50 mL) The combined organic layers were washed with saturated aqueous sodium chloride solution filtered concentrated in vacuo Silica gel chromatography (Gradient: 10% to 50% ethyl acetate in petroleum ether)

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

实验步骤: Potassium tert-butoxide (4.54 g, 40.5 mmol) was added to a solution of N2-(3-fluoro-4-methylphenyl)pyridine-2,3-diamine (C2) (from the previous step, 5.87 g, 24.4 mmol) and ethyl(cyclopropylamino)(oxo)acetate (P1) (6.36 g, 40.5 mmol) in 1-methylpyrrolidin-2-one (27 mL). The reaction mixture was heated at 120° C. for 10 minutes, cooled to room temperature and diluted with aqueous ammonium chloride solution. Tetrahydrofuran was added to assist solubilization, followed by ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo to provide the crude product (13.0 g). A portion of this material was used directly in the following step. LCMS m/z 329.0 [M+H]+. cooled to room temperature The organic layer was washed with saturated aqueous sodium chloride solution dried over magnesium sulfate filtered concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of cyclopropylamine (1.39 g, 24.3 mmol) and triethylamine (3.5 g, 35 mmol) was added drop-wise to a 0° C. solution of ethyl chloro(oxo)acetate (3.5 g, 26 mmol) in tetrahydrofuran (25 mL). The reaction mixture was stirred at 0° C. for 10 minutes and filtered; the filtrate was concentrated in vacuo to afford the product as a yellow solid Yield: 3.0 g, 19 mmol, 78%. 1H NMR (400 MHz, CDCl3) δ 7.14 (br s, 1H), 4.34 (q, J=7.2 Hz, 2H), 2.78-2.86 (m, 1H), 1.38 (t, J=7.2 Hz, 3H), 0.83-0.90 (m, 2H), 0.59-0.65 (m, 2H). filtered the filtrate was concentrated in vacuo