3,4,5-trifluorophenol

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: 1.0 M KOtBu in isopropanol (2 mL) is added to the solution of 3,4,5-trifluorophenol (0.29 g, 1.86 mmol) and stirred for 20 minutes at RT. To the resulting phenoxide solution is added a solution of 2-chloro-1-(6-chloropyridin-3-yl)-1,9-dihydro-6H-purin-6-one (0.5 g, 1.69 mmol) in dimethylacetamide (3 mL) and the resulting mixture is stirred overnight at 50° C. The resulting reaction mixture is cooled, quenched with saturated NH4Cl solution, extracted with DCM (2×50 mL) and dried (Na2SO4). The organic layer is filtered and concentrated under vacuum to afford the crude product as a light brown solid. The crude product is further purified by flash column chromatography using 5% MeOH/CH2Cl2 to afford the title compound as white solid. 1H NMR (300 MHz, CDCl3) δ 8.41 (s, 1H), 7.55-7.81 (m, 2H), 7.4 (brs, 1H), 6.71-7.02 (m, 2H), 3.85 (s, 3H). MS (M+1): 408.04; RT=1.48 min. The IC50 determined as described in Example 6 is 100 nanomolar or less. the resulting mixture is stirred overnight at 50° C The resulting reaction mixture is cooled quenched with saturated NH4Cl solution extracted with DCM (2×50 mL) dried (Na2SO4) The organic layer is filtered concentrated under vacuum to afford the crude product as a light brown solid The crude product is further purified by flash column chromatography

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-chloro-1-(4-fluorophenyl)-9-ethyl-1,9-dihydro-6H-purin-6-one (55.6 mg, 0.20 mmol) and 3,4,5-trifluorophenol (0.40 mmol) is heated to 140° C. for 36 h. After cooling to RT, the crude mixture is purified by preparative HPLC to give the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) 7.98 (1H, s), 7.55 (2H, m), 7.45 (2H, m), 7.34 (2H, m), 3.53 (3H, S). m/z=391.05 (M+1); RT=0.78 min. After cooling to RT the crude mixture is purified by preparative HPLC

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

実験手順: The general procedure of Example 3 was repeated using 3,4,5-trifluorophenol and 4-n-heptyl-4-phenyl-4-silacyclohexanecarboxylic acid, thereby obtaining the intended product. obtaining the intended product

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

実験手順: The general procedure of Example 3 was repeated using 3,4,5-trifluorophenol and 4-n-heptyl-4-phenyl-4-silacyclohexanecarboxylic acid, thereby obtaining the intended product. obtaining the intended product

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

実験手順: 400 g of 3,4,5-trifluorophenol are initially charged in 359 ml of 40% aqueous dimethylamine solution and cooled to 0° C. At 0-5° C., 243 ml of 37% aqueous formaldehyde solution are added dropwise within 90 min. Subsequently, the mixture is stirred at room temperature for 20 hours. The mixture is admixed with 600 ml of water and 500 ml of dichloromethane. The organic phase is removed, the aqueous phase is extracted once with dichloromethane, the combined organic phases are dried and the solvent is distilled off under reduced pressure. The crude product is taken up in 500 ml of water and adjusted to pH 1-2 with cooling in an ice bath using dilute hydrochloric acid. The acidic solution is extracted once with dichloromethane and subsequently adjusted to pH 8-9 with cooling in an ice bath using dilute sodium hydroxide solution. The alkaline reaction solution is extracted three times with dichloromethane, the combined organic phases are washed once with water and dried, and the solvent is removed under reduced pressure. The crude product is subsequently fractionally distilled under reduced pressure. 305 g (55% of theory) of a light yellow liquid having a boiling point of 96° C. at 10 mbar are obtained. The organic phase is removed the aqueous phase is extracted once with dichloromethane the combined organic phases are dried the solvent is distilled off under reduced pressure with cooling in an ice bath The acidic solution is extracted once with dichloromethane with cooling in an ice bath The alkaline reaction solution is extracted three times with dichloromethane the combined organic phases are washed once with water dried the solvent is removed under reduced pressure The crude product is subsequently fractionally distilled under reduced pressure are obtained

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

実験手順: The title compound was prepared by a procedure similar to that described for D4 starting from 2-fluoro-5-formylbenzonitrile (200 mg, 1.341 mmol) and 3,4,5-trifluorophenol.

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

実験手順: The title compound was prepared by a procedure similar to that described for D4 starting from 3,4-difluorobenzaldehyde and 3,4,5-trifluorophenol.

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

実験手順: The title compound was prepared by a procedure similar to that described for D4 starting from 3,4-difluorobenzaldehyde and 3,4,5-trifluorophenol.

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

実験手順: 1.31 g (7.5 mmol) of diethyl azodicarboxylate are added at 0° C. to 1.97 g (7.50 mmol) of triphenylphosphine in 30 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 0.5 hour. 1.11 g (7.50 mmol) of 3,4,5-trifluorophenol and 1.38 g (7.50 mmol) of trans-4-pentylcyclohexylmethanol are then added, and the mixture is stirred at room temperature for 18 hours. Evaporation of the solvent and chromatography on silica gel using hexane give 1.23 g of product. ##STR5## Phase sequence: X 14 (-26) I the mixture is stirred at room temperature for 18 hours Evaporation of the solvent and chromatography on silica gel

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

実験手順: A solution of 3,4,5-trifluorophenol (0.38 g, 2.55×10−3 mol) in dichloromethane (10 cm3) was added to a solution of N,N-dicyclohexylcarbodiimide (0.63 g, 3.06×10−3 mol), 4-(2-methoxyethoxy)benzoic acid (0.50 g, 2.55×10−3 mol), 4-(dimethylamino)pyridine (0.03 g 2.55×10−4mol) in dichloromethane (5 cm3), at 0° C. and then left to stirred overnight, filtered to remove precipitated material (DCU) and the filtrate evaporated down under reduced pressure. The crude product was purified by column chromatography on silica gel using a 1:1 dichloromethane-petroleum ether (40°-60° C.) mixture as eluent, followed by recrystalisation from ethanol. Yield 0.32 g (38%), GC purity (99.76%). left filtered to remove precipitated material (DCU) the filtrate evaporated down under reduced pressure The crude product was purified by column chromatography on silica gel using a 1:1 dichloromethane-petroleum ether (40°-60° C.) mixture as eluent followed by recrystalisation from ethanol

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

実験手順: 3,4,5-Trifluorophenol (14.81 g, 0.1 mol) was dissolved in glacial acetic acid (50 mL) and cooled to 4° C. while concentrated nitric acid (5 mL, 70%) was added dropwise over 15 min, during which time the color of the mixture becomes yellow. Upon complete addition of HNO3, the reaction mixture was allowed to warm to room temperature and stirred for an additional 30 min. TLC analysis of an aliquot extracted into ethyl acetate indicates that a new non-polar spot was formed and the complete consumption of starting material. The mixture was then diluted with ethyl acetate (200 mL), transferred to separatory funnel, and washed copiously with water (3×100 mL). The organic layer was finally washed with brine, dried over anhyd MgSO4, and evaporated under reduced pressure to afford crude product as a yellowish oil. (17.3 g, 90%). This crude material was used directly in the subsequent reaction described in Intermediate 6. 1H NMR (400 MHz, CDCl3): 6.84 (m, 1H, ArH), 10.28 (brs, 1H, OH). was added dropwise over 15 min, during which time the color of the mixture TLC analysis of an aliquot extracted into ethyl acetate was formed the complete consumption of starting material The mixture was then diluted with ethyl acetate (200 mL) transferred to separatory funnel washed copiously with water (3×100 mL) The organic layer was finally washed with brine dried over anhyd MgSO4 evaporated under reduced pressure to afford crude product as a yellowish oil