3-二甲基氨基-1-(4-氟苯基)-2-丙烯-1-酮

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

实验步骤: By using a method similar to that described in Example 35, but starting from 1-(4-fluorophenyl)-3-dimethylamino-2-propen-1-one (10 g), phosphorus oxychloride (4.76 cc), thiophenol (5.57 cc) and sodium cyanoborohydride (1.92 g), a residue is obtained which is taken up in chloroform. The solution is then adjusted to pH 10 by adding a concentrated aqueous solution of sodium hydroxide. The organic phase is separated and then the aqueous phase is extracted with methylene chloride. The organic phases are collected, dried over sodium sulphate, filtered and then evaporated to dryness under reduced pressured (2.7 kPa) at 30° C. A residue is obtained which is dissolved in isopropanol (30 cc). A 3N solution (12 cc) of hydrochloric acid gas in ethyl ether is added to this solution. The solid which precipitates is separated off by filtration and recrystallised from isopropanol (30 cc). In this way 1-dimethylamino-3-(4-fluorophenyl)-3-phenylthio-2-propene (E) hydrochloride (3.3 g) is obtained in the form of a white solid melting at 160° C. a residue is obtained which The organic phase is separated the aqueous phase is extracted with methylene chloride The organic phases are collected dried over sodium sulphate filtered evaporated to dryness under reduced pressured (2.7 kPa) at 30° C A residue is obtained which The solid which precipitates is separated off by filtration recrystallised from isopropanol (30 cc)

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

实验步骤: By using a method similar to that described in Example 35, but starting from 1-(4-fluorophenyl)-3-dimethylamino-2-propen-1-one (10 g), phosphorus oxychloride (4.76 cc), thiophenol (5.57 cc) and sodium cyanoborohydride (1.92 g), a residue is obtained which is taken up in chloroform. The solution is then adjusted to pH 10 by adding a concentrated aqueous solution of sodium hydroxide. The organic phase is separated and then the aqueous phase is extracted with methylene chloride. The organic phases are collected, dried over sodium sulphate, filtered and then evaporated to dryness under reduced pressured (2.7 kPa) at 30° C. A residue is obtained which is dissolved in isopropanol (30 cc). A 3N solution (12 cc) of hydrochloric acid gas in ethyl ether is added to this solution. The solid which precipitates is separated off by filtration and recrystallised from isopropanol (30 cc). In this way 1-dimethylamino-3-(4-fluorophenyl)-3-phenylthio-2-propene (E) hydrochloride (3.3 g) is obtained in the form of a white solid melting at 160° C. a residue is obtained which The organic phase is separated the aqueous phase is extracted with methylene chloride The organic phases are collected dried over sodium sulphate filtered evaporated to dryness under reduced pressured (2.7 kPa) at 30° C A residue is obtained which The solid which precipitates is separated off by filtration recrystallised from isopropanol (30 cc)

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

实验步骤: Part B. To a mixture of 3-carbamimidoyl-benzoic acid tert-butyl ester (220.2 mg, 0.94 mmol), 3-dimethylamino-1-(4-fluoro-phenyl)-propenone (182.6 mg, 0.95 mmol) and sodium hydride (39.2 mg, 1.63 mmol, 60% in hexanes) is added dry ethanol (5.0 mL). The resulting mixture is stirred at refluxing for 8 h until complete consumption of the starting material as determined by TLC. The solvent is removed, and the residue is added to 1N HCl (15 mL) to precipitate a yellow solid. The title product (137.8 mg, 41.3% yield) is produced after washing with water, then ethyl ether in sequence, m.p. 239-241° C. 1H NMR (300 MHz, DMSO-d6): δ 9.05 (1H, s), 8.97 (1H, d, J=5.0 Hz), 8.73 (1H, dd, J=7.7, 1.2 Hz), 8.38 (2H, m), 8.11 (1H, dd, J=8.0, 1.2 Hz), 8.04 (1H, d, J=5.3 Hz), 7.68 (1H, t, J=7.8 Hz), 7.43 (2H, m). MS (ES+): m/e 295.27. at refluxing for 8 h until complete consumption of the starting material The solvent is removed the residue is added to 1N HCl (15 mL) to precipitate a yellow solid

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

实验步骤: Part B. To a mixture of 3-carbamimidoyl-benzoic acid tert-butyl ester (220.2 mg, 0.94 mmol), 3-dimethylamino-1-(4-fluoro-phenyl)-propenone (182.6 mg, 0.95 mmol) and sodium hydride (39.2 mg, 1.63 mmol, 60% in hexanes) is added dry ethanol (5.0 mL). The resulting mixture is stirred at refluxing for 8 h until complete consumption of the starting material as determined by TLC. The solvent is removed, and the residue is added to 1N HCl (15 mL) to precipitate a yellow solid. The title product (137.8 mg, 41.3% yield) is produced after washing with water, then ethyl ether in sequence, m.p. 239-241° C. 1H NMR (300 MHz, DMSO-d6): δ 9.05 (1H, s), 8.97 (1H, d, J=5.0 Hz), 8.73 (1H, dd, J=7.7, 1.2 Hz), 8.38 (2H, m), 8.11 (1H, dd, J=8.0, 1.2 Hz), 8.04 (1H, d, J=5.3 Hz), 7.68 (1H, t, J=7.8 Hz), 7.43 (2H, m). MS (ES+): m/e 295.27. at refluxing for 8 h until complete consumption of the starting material The solvent is removed the residue is added to 1N HCl (15 mL) to precipitate a yellow solid

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

实验步骤: 2-Cyanoacetamide (4.31 g) and 3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one (9.00 g) were added in this order to a mixture of sodium hydride (60% oil, 4.10 g) and DMF (90 mL), and the resultant mixture was stirred at 105° C. for 2 hours. The solvent was distilled off. Water was added to the obtained residue, and then, the mixture was rendered acidic by the addition of acetic acid and stirred at 70° C. for 15 minutes. Methanol was added to the reaction mixture for suspension, and the deposited solid was washed with ethyl acetate to obtain the title compound (9.98 g). The solvent was distilled off Water was added to the obtained residue the mixture was rendered acidic by the addition of acetic acid Methanol was added to the reaction mixture for suspension the deposited solid was washed with ethyl acetate

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

实验步骤: A mixture of 5.0 g. of p-fluoroacetophenone and 10 ml. of dimethylformamide dimethylacetal is refluxed for 4 hours. Evaporation gives an oil which crystallizes with the addition of hexane to give the product, m.p. 83.5°-84° C. A mixture of 5.0 g Evaporation gives an oil which crystallizes with the addition of hexane to give the product, m.p. 83.5°-84° C.

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

实验步骤: Part B. To a mixture of 3-carbamimidoyl-benzoic acid tert-butyl ester (220.2 mg, 0.94 mmol), 3-dimethylamino-1-(4-fluoro-phenyl)-propenone (182.6 mg, 0.95 mmol) and sodium hydride (39.2 mg, 1.63 mmol, 60% in hexanes) is added dry ethanol (5.0 mL). The resulting mixture is stirred at refluxing for 8 h until complete consumption of the starting material as determined by TLC. The solvent is removed, and the residue is added to 1N HCl (15 mL) to precipitate a yellow solid. The title product (137.8 mg, 41.3% yield) is produced after washing with water, then ethyl ether in sequence, m.p. 239-241° C. 1H NMR (300 MHz, DMSO-d6): δ 9.05 (1H, s), 8.97 (1H, d, J=5.0 Hz), 8.73 (1H, dd, J=7.7, 1.2 Hz), 8.38 (2H, m), 8.11 (1H, dd, J=8.0, 1.2 Hz), 8.04 (1H, d, J=5.3 Hz), 7.68 (1H, t, J=7.8 Hz), 7.43 (2H, m). MS (ES+): m/e 295.27. at refluxing for 8 h until complete consumption of the starting material The solvent is removed the residue is added to 1N HCl (15 mL) to precipitate a yellow solid

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

实验步骤: 2-Cyanoacetamide (4.31 g) and 3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one (9.00 g) were added in this order to a mixture of sodium hydride (60% oil, 4.10 g) and DMF (90 mL), and the resultant mixture was stirred at 105 C for 2 hours. The solvent was distilled off. Water was added to the obtained residue, and then, the mixture was rendered acidic by the addition of acetic acid and stirred at 70 C for 15 minutes. Methanol was added to the reaction mixture for suspension, and the deposited solid was washed with ethyl acetate to obtain the title compound (9.98 g). The solvent was distilled off Water was added to the obtained residue the mixture was rendered acidic by the addition of acetic acid Methanol was added to the reaction mixture for suspension the deposited solid was washed with ethyl acetate

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

实验步骤: 2-Cyanoacetamide (4.31 g) and 3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one (9.00 g) were added in this order to a mixture of sodium hydride (60% oil, 4.10 g) and DMF (90 mL), and the resultant mixture was stirred at 105 C for 2 hours. The solvent was distilled off. Water was added to the obtained residue, and then, the mixture was rendered acidic by the addition of acetic acid and stirred at 70 C for 15 minutes. Methanol was added to the reaction mixture for suspension, and the deposited solid was washed with ethyl acetate to obtain the title compound (9.98 g). The solvent was distilled off Water was added to the obtained residue the mixture was rendered acidic by the addition of acetic acid Methanol was added to the reaction mixture for suspension the deposited solid was washed with ethyl acetate

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

实验步骤: By using a method similar to that described in Example 35, but starting from 1-(4-fluorophenyl)-3-dimethylamino-2-propen-1-one (10 g), phosphorus oxychloride (4.76 cc), thiophenol (5.57 cc) and sodium cyanoborohydride (1.92 g), a residue is obtained which is taken up in chloroform. The solution is then adjusted to pH 10 by adding a concentrated aqueous solution of sodium hydroxide. The organic phase is separated and then the aqueous phase is extracted with methylene chloride. The organic phases are collected, dried over sodium sulphate, filtered and then evaporated to dryness under reduced pressure (2.7 kPa) at 30° C. A residue is obtained which is dissolved in isopropanol (30 cc). A 3N solution (12 cc) of hydrochloric acid gas in ethyl ether is added to this solution. The solid which precipitates is separated off by filtration and recrystallised from isopropanol (30 cc). In this way 1-dimethylamino-3-(4-fluorophenyl)-3-phenylthio-2-propene (E) hydrochloride (3.3 g) is obtained in the form of a white solid melting at 160° C. a residue is obtained which The organic phase is separated the aqueous phase is extracted with methylene chloride The organic phases are collected dried over sodium sulphate filtered evaporated to dryness under reduced pressure (2.7 kPa) at 30° C A residue is obtained which The solid which precipitates is separated off by filtration recrystallised from isopropanol (30 cc)

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

实验步骤: By using a method similar to that described in Example 35, but starting from 1-(4-fluorophenyl)-3-dimethylamino-2-propen-1-one (10 g), phosphorus oxychloride (4.76 cc), thiophenol (5.57 cc) and sodium cyanoborohydride (1.92 g), a residue is obtained which is taken up in chloroform. The solution is then adjusted to pH 10 by adding a concentrated aqueous solution of sodium hydroxide. The organic phase is separated and then the aqueous phase is extracted with methylene chloride. The organic phases are collected, dried over sodium sulphate, filtered and then evaporated to dryness under reduced pressured (2.7 kPa) at 30° C. A residue is obtained which is dissolved in isopropanol (30 cc). A 3N solution (12 cc) of hydrochloric acid gas in ethyl ether is added to this solution. The solid which precipitates is separated off by filtration and recrystallised from isopropanol (30 cc). In this way 1-dimethylamino-3-(4-fluorophenyl)-3-phenylthio-2-propene (E) hydrochloride (3.3 g) is obtained in the form of a white solid melting at 160° C. a residue is obtained which The organic phase is separated the aqueous phase is extracted with methylene chloride The organic phases are collected dried over sodium sulphate filtered evaporated to dryness under reduced pressured (2.7 kPa) at 30° C A residue is obtained which The solid which precipitates is separated off by filtration recrystallised from isopropanol (30 cc)

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

实验步骤: 2-Cyanoacetamide (4.31 g) and 3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one (9.00 g) were added in this order to a mixture of sodium hydride (60% oil, 4.10 g) and DMF (90 mL), and the resultant mixture was stirred at 105° C. for 2 hours. The solvent was distilled off. Water was added to the obtained residue, and then, the mixture was rendered acidic by the addition of acetic acid and stirred at 70° C. for 15 minutes. Methanol was added to the reaction mixture for suspension, and the deposited solid was washed with ethyl acetate to obtain the title compound (9.98 g). The solvent was distilled off Water was added to the obtained residue the mixture was rendered acidic by the addition of acetic acid Methanol was added to the reaction mixture for suspension the deposited solid was washed with ethyl acetate