(3,4,5-trifluorophenyl)methanamine

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

実験手順: The title compound or its salt was prepared by a procedure similar to that described for E59 starting from (3,4,5-trifluorophenyl)methanamine and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.

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

実験手順: The title compound or its salt was prepared by a procedure similar to that described for E59 starting from (3,4,5-trifluorophenyl)methanamine and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of intermediate 59 (0.5 g, 1.36 mmol), 3,4,5-trifluorobenzylamine (0.66 g, 4.0 mmol) and MeOH (0.2 mL) is heated at 100° C. for 2 days. The reaction mixture is cooled to RT, and the mixture is purified by chromatography on silica gel; gradient elution with heptane:EtOAc (70:30-50:50) gives 0.44 g of the product 83. 1H NMR (CDCl3) δ 7.59 (s, 1 H), 7.20-7.05 (m, 2 H), 7.05-6.90 (m, 8 H), 6.80-6.70 (m, 2 H), 5.45-5.30 (m, 2 H), 4.70-4.50 (m, 2 H), 1.16 (s, 9 H); MS: m/z 482 (M++1). The reaction mixture is cooled to RT the mixture is purified by chromatography on silica gel gradient elution with heptane:EtOAc (70:30-50:50)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of intermediate 59 (0.5 g, 1.36 mmol), 3,4,5-trifluorobenzylamine (0.66 g, 4.0 mmol) and MeOH (0.2 mL) is heated at 100° C. for 2 days. The reaction mixture is cooled to RT, and the mixture is purified by chromatography on silica gel; gradient elution with heptane:EtOAc (70:30-50:50) gives 0.44 g of the product 83. 1H NMR (CDCl3) δ 7.59 (s, 1 H), 7.20-7.05 (m, 2 H), 7.05-6.90 (m, 8 H), 6.80-6.70 (m, 2 H), 5.45-5.30 (m, 2 H), 4.70-4.50 (m, 2 H), 1.16 (s, 9 H); MS: m/z 482 (M++1). The reaction mixture is cooled to RT the mixture is purified by chromatography on silica gel gradient elution with heptane:EtOAc (70:30-50:50)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chloro-N-((3-(trifluoromethyl)-1H-pyrazol-5-yl)carbamothioyl)benzamide (500 mg, 1.43 mmol) was dissolved in methanol (5 mL) and 3,4,5-trifluorobenzylamine (462 mg, 2.87 mmol) was added followed by N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (550 mg, 2.87 mmol). The reaction was stirred at 50° C. for 30 minutes. The crude mixture was then partitioned between water and ethyl acetate. The organic layer was washed with brine, and dried over sodium sulfate, then purified by chromatography (gradient: 95:5 hexanes:EtOAc to 7:3 hexanes:EtOAc). (Z)-4-Chloro-N-(((3,4,5-trifluorobenzyl)amino)((3-(trifluoromethyl)-1H-pyrazol-5-yl)amino)methylene)benzamide was obtained as a solid (221 mg, 32% yield). MS (ES+) 475.8. The crude mixture was then partitioned between water and ethyl acetate The organic layer was washed with brine dried over sodium sulfate purified by chromatography (gradient: 95:5 hexanes:EtOAc to 7:3 hexanes:EtOAc)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chloro-N-((3-(trifluoromethyl)-1H-pyrazol-5-yl)carbamothioyl)benzamide (500 mg, 1.43 mmol) was dissolved in methanol (5 mL) and 3,4,5-trifluorobenzylamine (462 mg, 2.87 mmol) was added followed by N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (550 mg, 2.87 mmol). The reaction was stirred at 50° C. for 30 minutes. The crude mixture was then partitioned between water and ethyl acetate. The organic layer was washed with brine, and dried over sodium sulfate, then purified by chromatography (gradient: 95:5 hexanes:EtOAc to 7:3 hexanes:EtOAc). (Z)-4-Chloro-N-(((3,4,5-trifluorobenzyl)amino)((3-(trifluoromethyl)-1H-pyrazol-5-yl)amino)methylene)benzamide was obtained as a solid (221 mg, 32% yield). MS (ES+) 475.8. The crude mixture was then partitioned between water and ethyl acetate The organic layer was washed with brine dried over sodium sulfate purified by chromatography (gradient: 95:5 hexanes:EtOAc to 7:3 hexanes:EtOAc)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of intermediate 59 (0.5 g, 1.36 mmol), 3,4,5-trifluorobenzylamine (0.66 g, 4.0 mmol) and MeOH (0.2 mL) is heated at 100° C. for 2 days. The reaction mixture is cooled to RT, and the mixture is purified by chromatography on silica gel; gradient elution with heptane: EtOAc (70:30-50:50) gives 0.44 g of the product 83. 1H NMR (CDCl3) δ 7.59 (s, 1H), 7.20-7.05 (m, 2H), 7.05-6.90 (m, 8H), 6.80-6.70 (m, 2H), 5.45-5.30 (m, 2H), 4.70-4.50 (m, 2H), 1.16 (s, 9H); MS: m/z 482 (M++1). The reaction mixture is cooled to RT the mixture is purified by chromatography on silica gel gradient elution with heptane: EtOAc (70:30-50:50)

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

実験手順: According to the method of Example 160, 2-cyano-2-(3,4-dichloro-5-oxo-2,5-dihydrofuran-2-yl)acetamide was reacted with 1-(3,4,5-trifluorophenyl)methanamine to give the title compound.

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

実験手順: The title compound or its salt was prepared by a procedure similar to that described for E59 starting from (3,4,5-trifluorophenyl)methanamine and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of intermediate 59 (0.5 g, 1.36 mmol), 3,4,5-trifluorobenzylamine (0.66 g, 4.0 mmol) and MeOH (0.2 mL) is heated at 100° C. for 2 days. The reaction mixture is cooled to RT, and the mixture is purified by chromatography on silica gel; gradient elution with heptane:EtOAc (70:30-50:50) gives 0.44 g of the product 83. 1H NMR (CDCl3) δ 7.59 (s, 1 H), 7.20-7.05 (m, 2 H), 7.05-6.90 (m, 8 H), 6.80-6.70 (m, 2 H), 5.45-5.30 (m, 2 H), 4.70-4.50 (m, 2 H), 1.16 (s, 9 H); MS: m/z 482 (M++1). The reaction mixture is cooled to RT the mixture is purified by chromatography on silica gel gradient elution with heptane:EtOAc (70:30-50:50)