1,1,1,5,5,5-六氟戊烷-2,4-二酮

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

实验步骤: At 110° C., 50 mg (19 mmol) of 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamidine from Example 25A and 42 mg (20 mmol) of 1,1,1,5,5,5-hexafluoroacetylacetone are heated for 5 h. Chromatography gives 33 mg (40.3% of theory) of the title compound.

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

实验步骤: Crude 5-(2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoyl)hexahydro-pyrrolo[3,4-c]pyrrole-2(1H)-carboximidamide—TFA salt (66 mg) was diluted with n-butanol (4 mL) and treated with sodium methoxide (51.9 mg, 0.961 mmol). The reaction is heated to reflux for 1 hour, then cooled and 1,1,1,5,5,5-hexafluoropentane-2,4-dione (400 mg, 1.92 mmol) is added prior to re-heating the reaction to reflux for 19 hours. The mixture was then cooled and concentrated, then diluted with DCM and saturated sodium bicarbonate. Extract with DCM and concentrate. Reverse phase HPLC gave the title compound (4.6 mg). MS (ESI): mass calculated for C21H16F7N7O, 515.39; m/z found 416.2 [M+H]+. Rotamers observed in 1H NMR. The reaction is heated to reflux for 1 hour cooled to re-heating the reaction to reflux for 19 hours The mixture was then cooled concentrated diluted with DCM and saturated sodium bicarbonate Extract with DCM concentrate

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

实验步骤: Crude 5-(2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoyl)hexahydro-pyrrolo[3,4-c]pyrrole-2(1H)-carboximidamide—TFA salt (66 mg) was diluted with n-butanol (4 mL) and treated with sodium methoxide (51.9 mg, 0.961 mmol). The reaction is heated to reflux for 1 hour, then cooled and 1,1,1,5,5,5-hexafluoropentane-2,4-dione (400 mg, 1.92 mmol) is added prior to re-heating the reaction to reflux for 19 hours. The mixture was then cooled and concentrated, then diluted with DCM and saturated sodium bicarbonate. Extract with DCM and concentrate. Reverse phase HPLC gave the title compound (4.6 mg). MS (ESI): mass calculated for C21H16F7N7O, 515.39; m/z found 416.2 [M+H]+. Rotamers observed in 1H NMR. The reaction is heated to reflux for 1 hour cooled to re-heating the reaction to reflux for 19 hours The mixture was then cooled concentrated diluted with DCM and saturated sodium bicarbonate Extract with DCM concentrate

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

实验步骤: A solution of 20.8 g (0.100 mol) of 1,1,1,5,5,5-hexafluoro-2,4-pentanedione and 20.6 g (0.100 mol) of 3-amino-5-benzylthio-1,2,4-triazole in 150 ml of glacial acetic acid was heated at reflux for 14 hours. The solution was cooled to room temperature and poured over ice. The solid which separated was collected by filtration, washed with water and dried in vacuo to yield 35.5 g (94%) of the desired product as a pale yellow solid, m.p. 78.5°-80.5° C. IR, 1H NMR and 19F NMR spectra were in agreement with the assigned structure. at reflux for 14 hours poured over ice The solid which separated was collected by filtration washed with water dried in vacuo

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

实验步骤: A solution of 20.8 g (0.100 mol) of 1,1,1,5,5,5-hexafluoro-2,4-pentanedione and 20.6 g (0.100 mol) of 3-amino-5-benzylthio-1,2,4-triazole in 150 ml of glacial acetic acid was heated at reflux for 14 hours. The solution was cooled to room temperature and poured over ice. The solid which separated was collected by filtration, washed with water and dried in vacuo to yield 35.5 g (94%) of the desired product as a pale yellow solid, m.p. 78.5°-80.5° C. IR, 1H NMR and 19F NMR spectra were in agreement with the assigned structure. at reflux for 14 hours poured over ice The solid which separated was collected by filtration washed with water dried in vacuo

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

实验步骤: A solution of 20.8 g (0.100 mol) of 1,1,1,5,5,5-hexafluoro-2,4-pentanedione and 20.6 g (0.100 mol) of 3-amino-5-benzylthio-1,2,4-triazole in 150 ml of glacial acetic acid was heated at reflux for 14 hours. The solution was cooled to room temperature and poured over ice. The solid which separated was collected by filtration, washed with water and dried in vacuo to yield 35.5 g (94%) of the desired product as a pale yellow solid, m.p. 78.5°-80.5° C. IR, 1H NMR and 19F NMR spectra were in agreement with the assigned structure. at reflux for 14 hours poured over ice The solid which separated was collected by filtration washed with water dried in vacuo

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1,1,1,5,5,5-hexafluoro-pentane-2,4-dione (3.16 g, 15.2 mmol) and 4-hydrazinobenzoic acid hydrochloride (2.86 g, 15.2 mmol) in ethanol (5 mL) was stirred at 100° C. in a sealed tube for 4 hours. The mixture was cooled to room temperature and the solvent was removed under reduced pressure. The residue was purified by chromatography (SiO2, 4:1 to 3:1 hexane/EtOAc) to give 4-(3,5-bis-trifluoromethyl-pyrazol-1-yl)-benzoic acid ethyl ester, (3.1 g, 58% yield) as a syrup: 1H-NMR (CDCl3) δ 1.40 (t, 3H, J=7), 4.35-4.50 (m, 2H), 7.10 (s, 1H), 7.60 (d, 2H, J=7), 8.21 (d, 2H, J=7) ppm. The mixture was cooled to room temperature the solvent was removed under reduced pressure The residue was purified by chromatography (SiO2, 4:1 to 3:1 hexane/EtOAc)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1,1,1,5,5,5-hexafluoro-pentane-2,4-dione (3.16 g, 15.2 mmol) and 4-hydrazinobenzoic acid hydrochloride (2.86 g, 15.2 mmol) in ethanol (5 mL) was stirred at 100° C. in a sealed tube for 4 hours. The mixture was cooled to room temperature and the solvent was removed under reduced pressure. The residue was purified by chromatography (SiO2, 4:1 to 3:1 hexane/EtOAc) to give 4-(3,5-bis-trifluoromethyl-pyrazol-1-yl)-benzoic acid ethyl ester, (3.1 g, 58% yield) as a syrup: 1H-NMR (CDCl3) δ 1.40 (t, 3H, J=7), 4.35-4.50 (m, 2H), 7.10 (s, 1H), 7.60 (d, 2H, J=7), 8.21 (d, 2H, J=7) ppm. The mixture was cooled to room temperature the solvent was removed under reduced pressure The residue was purified by chromatography (SiO2, 4:1 to 3:1 hexane/EtOAc)

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

实验步骤: Using hexafluoroacetylacetone and 3-nitrophenylhydrazine hydrochloride as the raw materials, the same operation as the Example 538(1) gave the title compound.

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

实验步骤: A solution of 20.8 g (0.100 mol) of 1,1,1,5,5,5-hexafluoro-2,4-pentanedione and 20.6 g (0.100 mol) of 3-amino-5-benzylthio-1,2,4-triazole in 150 ml of glacial acetic acid was heated at reflux for 14 hours. The solution was cooled to room temperature and poured over ice. The solid which separated was collected by filtration, washed with water and dried in vacuo to yield 35.5 g (94%) of the desired product as a pale yellow solid, m.p. 78.5°-80.5° C. IR, 1H NMR and 19F NMR spectra were in agreement with the assigned structure. at reflux for 14 hours poured over ice The solid which separated was collected by filtration washed with water dried in vacuo

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

实验步骤: A solution of 20.8 g (0.100 mol) of 1,1,1,5,5,5-hexafluoro-2,4-pentanedione and 20.6 g (0.100 mol) of 3-amino-5-benzylthio-1,2,4-triazole in 150 ml of glacial acetic acid was heated at reflux for 14 hours. The solution was cooled to room temperature and poured over ice. The solid which separated was collected by filtration, washed with water and dried in vacuo to yield 35.5 g (94%) of the desired product as a pale yellow solid, m.p. 78.5°-80.5° C. IR, 1H NMR and 19F NMR spectra were in agreement with the assigned structure. at reflux for 14 hours poured over ice The solid which separated was collected by filtration washed with water dried in vacuo

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

实验步骤: A process as claimed in claim 1 wherein 2,6-diaminopyridine is reacted with 1,1,1,5,5,5-hexafluoroacetylacetone to provide 2-amino-5,7-di(trifluoromethyl)-1,8-naphthyridine.