3-ethynyl-4-fluoroaniline

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: The product is prepared according to the procedure described in example 5, using 204 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate, 211 mg of 3-ethynyl-4-fluoroaniline, and 195 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride in a mixture of 0.126 ml of pyridine and 3 ml of N,N-dimethylformamide. 200 mg of N-(3-ethynyl-4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a white solid, the characteristics of which are the following: The product is prepared

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

実験手順: The product is prepared according to the procedure described in example 5, using 204 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate, 211 mg of 3-ethynyl-4-fluoroaniline, and 195 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride in a mixture of 0.126 ml of pyridine and 3 ml of N,N-dimethylformamide. 200 mg of N-(3-ethynyl-4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a white solid, the characteristics of which are the following: The product is prepared

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 16 mg of potassium carbonate are added to a solution of 360 mg of 4-fluoro-3-[(trimethylsilyl)ethynyl]aniline in 5 ml of methanol. After stirring over night under argon and at a temperature in the region of 20° C., the medium is concentrated to dryness under reduced pressure, then taken up in 8 ml of water and neutralized with a few drops of hydrochloric acid (1 N), and then extracted three times with diethyl ether. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. 225 mg of 3-ethynyl-4-fluoroaniline are obtained in the form of a brown oil, the characteristics of which are the following: the medium is concentrated to dryness under reduced pressure extracted three times with diethyl ether The combined organic phases are dried over anhydrous magnesium sulphate filtered concentrated to dryness under reduced pressure

反応条件: temp:83.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 4-chloro-7-methoxyquinazolin-6-yl acetate (4.31 g), 3-ethynyl-4-fluoroaniline (2.77 g) and isopropanol (65 mL) was stirred at 83° C. overnight. The reaction mixture was cooled to room temperature and filtered, the residue was washed with 100 mL of isopropanol and dried to afford the desired compound as a solid (5.29 g, 88.30%). The reaction mixture was cooled to room temperature filtered the residue was washed with 100 mL of isopropanol dried

反応条件: temp:83.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 4-chloro-7-methoxyquinazolin-6-yl acetate (4.31 g), 3-ethynyl-4-fluoroaniline (2.77 g) and isopropanol (65 mL) was stirred at 83° C. overnight. The reaction mixture was cooled to room temperature and filtered, the residue was washed with 100 mL of isopropanol and dried to afford the desired compound as a solid (5.29 g, 88.30%). The reaction mixture was cooled to room temperature filtered the residue was washed with 100 mL of isopropanol dried

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

実験手順: A heterogeneous mixture of 6-fluoropyrido[3,4-d]pyrimidin-4(3H)-one (200) (1.65 g, 10.0 mmol), thionyl chloride (20 mL) and a catalytic amount of DMF (2 drops) was stirred under reflux for 1 h to give a homogeneous mixture. It was evaporated under reduced pressure at 45° C. (bath temperature) to give a light brown solid. To this solid was added a solution of 3-ethynyl-4-fluoroaniline (J. Org. Chem., 1981, 46, 2280-2286) (1.49 g, 11.0 mmol) and dry DMA (15 mL). The residue of 3-ethynyl-4-fluoroaniline was washed down with more DMA (2×2 mL). The reaction mixture was stirred at room temperature for 45 h. It was poured into water (300 mL). The pH was adjusted to ca. 9 using an aqueous solution of Na2CO3 at room temperature. Petroleum ether (300 mL) was added and stirred at room temperature for 30 min. The petroleum ether layer was decanted. It was repeated once more with petroleum ether (300 mL). The solid was collected by filtration and washed with water (5×50 mL); ethyl acetate/petroleum ether (1:10) (4×50 mL) and dried to give N-(3-ethynyl-4-fluorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine (208) (2.39 g, 85%) as a pale brown solid, mp 223-226° C.; 1H NMR δ [(CD3)2SO] 10.10 (s, 1H), 8.96 (s, 1H), 8.73 (s, 1H), 8.24 (br s, 1H),), 8.12 (dd, J=6.4, 2.8 Hz, 1H), 7.96-7.88 (m, 1H), 7.39 (t, J=9.1 Hz, 1H), 4.54 (s, 1H). Anal. Calcd for C15H8F2N4.1.8H2O: C, 57.25; H, 3.72; N, 17.80. Found C, 57.27; H, 3.49; N, 17.90. under reflux for 1 h to give a homogeneous mixture It was evaporated under reduced pressure at 45° C. (bath temperature) to give a light brown solid The residue of 3-ethynyl-4-fluoroaniline was washed down with more DMA (2×2 mL) It was poured into water (300 mL) at room temperature Petroleum ether (300 mL) was added stirred at room temperature for 30 min The petroleum ether layer was decanted The solid was collected by filtration washed with water (5×50 mL) ethyl acetate/petroleum ether (1:10) (4×50 mL) and dried

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: To a solution of 3-ethynyl-4-fluoroaniline (220 mg, 1.62 mmol) in ethyl acetate (10 mL) was added 10% palladium on carbon (wet). The resulting mixture was subjected to an atmosphere of hydrogen for approximately 1 h. The palladium on carbon was removed by filtration through celite. The filtrate was concentrated in vacuo to provide 3-ethyl-4-fluoroaniline (154 mg, 1.11 mmol, 69% yield) as a brown oil. 1H NMR (400 MHz, CDCl3): 6.77 (dd, 1H), 6.50 (dd, 1H), 6.45-6.41 (m, 1H), 3.47 (br s, 2H), 2.57 (q, 2H), 1.19 (t, 3H); MS (EI) for C8H10FN: 140 (MH+). The palladium on carbon was removed by filtration through celite The filtrate was concentrated in vacuo

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

実験手順: To a solution of 3-ethynyl-4-fluoroaniline (220 mg, 1.62 mmol) in ethyl acetate (10 mL) was added 10% palladium on carbon (wet). The resulting mixture was subjected to an atmosphere of hydrogen for approximately 1 h. The palladium on carbon was removed by filtration through celite. The filtrate was concentrated in vacuo to provide 3-ethyl-4-fluoroaniline (154 mg, 1.11 mmol, 69% yield) as a brown oil. 1H NMR (400 MHz, CDCl3): 6.77 (dd, 1H), 6.50 (dd, 1H), 6.45-6.41 (m, 1H), 3.47 (br s, 2H), 2.57 (q, 2H), 1.19 (t, 3H); MS (EI) for C8H10FN: 140 (MH+). The palladium on carbon was removed by filtration through celite The filtrate was concentrated in vacuo

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

実験手順: To a solution of 3-ethynyl-4-fluoroaniline (220 mg, 1.62 mmol) in ethyl acetate (10 mL) was added 10% palladium on carbon (wet). The resulting mixture was subjected to an atmosphere of hydrogen for approximately 1 h. The palladium on carbon was removed by filtration through celite. The filtrate was concentrated in vacuo to provide 3-ethyl-4-fluoroaniline (154 mg, 1.11 mmol, 69% yield) as a brown oil. 1H NMR (400 MHz, CDCl3): 6.77 (dd, 1H), 6.50 (dd, 1H), 6.45-6.41 (m, 1H), 3.47 (br s, 2H), 2.57 (q, 2H), 1.19 (t, 3H); MS (EI) for C8H10FN: 140 (MH+). The palladium on carbon was removed by filtration through celite The filtrate was concentrated in vacuo

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

実験手順: To a solution of 3-ethynyl-4-fluoroaniline (220 mg, 1.62 mmol) in ethyl acetate (10 mL) was added 10% palladium on carbon (wet). The resulting mixture was subjected to an atmosphere of hydrogen for approximately 1 h. The palladium on carbon was removed by filtration through celite. The filtrate was concentrated in vacuo to provide 3-ethyl-4-fluoroaniline (154 mg, 1.11 mmol, 69% yield) as a brown oil. 1H NMR (400 MHz, CDCl3): 6.77 (dd, 1H), 6.50 (dd, 1H), 6.45-6.41 (m, 1H), 3.47 (br s, 2H), 2.57 (q, 2H), 1.19 (t, 3H); MS (EI) for C8H10FN: 140 (MH+). The palladium on carbon was removed by filtration through celite The filtrate was concentrated in vacuo