3-PHENYL-1,1,1-TRIFLUOROPROPAN-2-ONE

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 100 mg (0.44 mmol) of 1-(4-fluorophenyl)-1H-indazol-5-ylamine in 5 mL of dichloromethane was added 60 μL (1.04 mmol) of 1,1,1-trifluoro-3-phenylpropan-2-one, 70 μL (0.97 mmol) of triethylamine followed by 130 μL (1.02 mmol) of TiCl4. The mixture was stirred for 20 hours and then MeOH was added followed by 200 mg (5.29 mmol) of sodium borohydride. After 1 hour, the mixture was diluted 50 mL of 1N aqueous NaOH and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude material was purified by Combiflash chromatography using a EtOAc-hexanes (0-70% gradient) to provide 70 mg (37%) of [144-fluorophenyl)-1H-indazol-5-yl]-((E)-2-phenyl-1-trifluoromethylvinyl)amine as a yellow solid. After 1 hour extracted with ethyl acetate The combined organic layers were washed with brine dried over sodium sulfate concentrated in vacuo The crude material was purified by Combiflash chromatography

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

実験手順: To a solution of 100 mg (0.44 mmol) of 1-(4-fluorophenyl)-1H-indazol-5-ylamine in 5 mL of dichloromethane was added 60 μL (1.04 mmol) of 1,1,1-trifluoro-3-phenylpropan-2-one, 70 μL (0.97 mmol) of triethylamine followed by 130 μL (1.02 mmol) of TiCl4. The mixture was stirred for 20 hours and then MeOH was added followed by 200 mg (5.29 mmol) of sodium borohydride. After 1 hour, the mixture was diluted 50 mL of 1N aqueous NaOH and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude material was purified by Combiflash chromatography using a EtOAc-hexanes (0-70% gradient) to provide 70 mg (37%) of [144-fluorophenyl)-1H-indazol-5-yl]-((E)-2-phenyl-1-trifluoromethylvinyl)amine as a yellow solid. After 1 hour extracted with ethyl acetate The combined organic layers were washed with brine dried over sodium sulfate concentrated in vacuo The crude material was purified by Combiflash chromatography

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

実験手順: A mixture of 2-amino-5-bromobenzoic acid (3.01 g, 13.9 mmol), 1,1,1-trifluoro-3-phenylpropan-2-one (3.11 g, 16.5 mmol), and Eaton's reagent (9.3 mL) in a sealed tube was heated at 100° C. for 4 hours. The reaction mixture was then allowed to cool to room temperature, water was added slowly, and the mixture was stirred vigorously for about 15 min. The precipitated solid was filtered, washed with water, and dried to give the title compound. to cool to room temperature The precipitated solid was filtered washed with water dried

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A yellow solution of 1-(2-amino-5-bromophenyl)-2,2,2-trifluoroethanone (1.32 g, 4.94 mmol, Intermediate 8, step b) and 1,1,1-trifluoro-3-phenylpropan-2-one (0.980 g, 5.21 mmol) in DMF (4.95 mL) was treated with tributylamine (1.23 mL, 5.19 mmol) and stirred at 130° C. under air (capped) for 2 hours. The homogeneous orange solution was then cooled to room temperature and partitioned with ether (8 mL) and 1 M NaH2PO4 (8 mL). The organic layer was washed with 1 M NaH2PO4 (1×8 mL), dried (Na2SO4), filtered, and concentrated, and the residue was flash chromatographed with a heptane to 30% DCM/heptane gradient to yield the title compound as a nearly colorless oil. The homogeneous orange solution was then cooled to room temperature partitioned with ether (8 mL) and 1 M NaH2PO4 (8 mL) The organic layer was washed with 1 M NaH2PO4 (1×8 mL) dried (Na2SO4) filtered concentrated chromatographed with a heptane to 30% DCM/heptane gradient

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A yellow solution of 1-(2-amino-5-bromophenyl)-2,2,2-trifluoroethanone (1.32 g, 4.94 mmol, Intermediate 8, step b) and 1,1,1-trifluoro-3-phenylpropan-2-one (0.980 g, 5.21 mmol) in DMF (4.95 mL) was treated with tributylamine (1.23 mL, 5.19 mmol) and stirred at 130° C. under air (capped) for 2 hours. The homogeneous orange solution was then cooled to room temperature and partitioned with ether (8 mL) and 1 M NaH2PO4 (8 mL). The organic layer was washed with 1 M NaH2PO4 (1×8 mL), dried (Na2SO4), filtered, and concentrated, and the residue was flash chromatographed with a heptane to 30% DCM/heptane gradient to yield the title compound as a nearly colorless oil. The homogeneous orange solution was then cooled to room temperature partitioned with ether (8 mL) and 1 M NaH2PO4 (8 mL) The organic layer was washed with 1 M NaH2PO4 (1×8 mL) dried (Na2SO4) filtered concentrated chromatographed with a heptane to 30% DCM/heptane gradient

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

実験手順: A mixture of 2-amino-5-iodobenzoic acid (5.20 g, 19.8 mmol), 1,1,1-trifluoro-3-phenylpropan-2-one (3.95 g, 21.0 mmol), and Eaton's reagent (12 mL) in a sealed tube was heated at 100° C. for 2 hours. More 1,1,1-trifluoro-3-phenylpropan-2-one (1.60 g, 8.50 mmol) was added and the mixture was heated for another 2 hours. The reaction was then cooled to room temperature, ice water was added, and the mixture was stirred vigorously for about 20 min. 50% NaOH and conc. NH4OH solution were added until pH was 9. Some gummy dark brown material formed. After the addition of CH2Cl2, the gummy material became fluffy solid. This solid was filtered, washed with water and Et2O, and air dried to give the title compound. the mixture was heated for another 2 hours The reaction was then cooled to room temperature Some gummy dark brown material formed This solid was filtered washed with water and Et2O, and air dried

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., DMF (4.3 mL) is carefully treated with phosphoroxychloride (2.8 mL) and the mixture is stirred at rt for 20 min before 1,1,1-trifluoro-3-phenyl-propan-2-one (1.55 mL, 10 mmol) is slowly added. The reaction mixture is stirred for 2 h at 45° C. and 18 h at rt, diluted with sat. aq. Na-acetate solution (20 mL) and water (40 mL) and extracted with diethyl ether. The organic phase is separated, washed with sat. aq. NaHCO3-solution, dried over Na2SO4 and evaporated to give 3-chloro-4,4,4-trifluoro-2-phenyl-but-2-enal (2.20 g) as a pale yellow oil. is slowly added extracted with diethyl ether The organic phase is separated washed with sat. aq. NaHCO3-solution dried over Na2SO4 evaporated

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

実験手順: To a solution of 100 mg (0.44 mmol) of 1-(4-fluorophenyl)-1H-indazol-5-ylamine in 5 mL of dichloromethane was added 60 μL (1.04 mmol) of 1,1,1-trifluoro-3-phenylpropan-2-one, 70 μL (0.97 mmol) of triethylamine followed by 130 μL (1.02 mmol) of TiCl4. The mixture was stirred for 20 hours and then MeOH was added followed by 200 mg (5.29 mmol) of sodium borohydride. After 1 hour, the mixture was diluted 50 mL of 1N aqueous NaOH and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude material was purified by Combiflash chromatography using a EtOAc-hexanes (0-70% gradient) to provide 70 mg (37%) of [144-fluorophenyl)-1H-indazol-5-yl]-((E)-2-phenyl-1-trifluoromethylvinyl)amine as a yellow solid. After 1 hour extracted with ethyl acetate The combined organic layers were washed with brine dried over sodium sulfate concentrated in vacuo The crude material was purified by Combiflash chromatography

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,1,1-trifluoro-3-phenylpropanone (0.50 mL, 3.2 mmol) was dissolved in 5 mL of diethyl ether and the mixture was cooled to 0° C. Bromine (0.16 mL, 3.2 mmoL) was added and the mixture was stirred for 18 h and allowed to warm to rt. The solvent was removed to provide a 2:1 mixture of Example A176a as a starting material which was used in the subsequent reaction without further purification. to warm to rt The solvent was removed to provide was used in the subsequent reaction without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,1,1-trifluoro-3-phenylpropanone (0.50 mL, 3.2 mmol) was dissolved in 5 mL of diethyl ether and the mixture was cooled to 0° C. Bromine (0.16 mL, 3.2 mmoL) was added and the mixture was stirred for 18 h and allowed to warm to rt. The solvent was removed to provide a 2:1 mixture of Example A176a as a starting material which was used in the subsequent reaction without further purification. to warm to rt The solvent was removed to provide was used in the subsequent reaction without further purification