1-(2,3,4-trichlorophenyl)ethanone

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: Using the method described in Example 30 by employing [1-(2,3,4-trichlorophenyl]vinyl]pyrrolidine (freshly prepared before use from 2′,3′,4′-trichloro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.00 g, 3.64 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (0.80 g, 3.64 mmol), N,N-diisopropylethylamine (0.6 mL, 3.64 mmol), piperidine (0.6 mL, 5.80 mmol), NEt3 (0.7 mL) and SnCl2 (11 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 125 mg (9%) of 2-methyl-4-piperidyl-6-(2,3,4-trichlorophenyl)pyrrolo[3,2-d]pyrimidine as a brown colored oil. This material (125 mg, 0.32 mmol) was dissolved in 5:1 EtOAc/MeOH (15 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.40 mL, 0.40 mmol). The solution was left to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 55 mg (4%) of the title compound as beige colored needles. Mp: 264-266° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.71 (br s, 6), 2.58 (s, 3), 4.03 (s, 4), 6.78 (s, 1), 7.71 (d, 2, J=8.4), 7.88 (d, 2, J=8.5), 12.40 (s, 1), 14.39 (s, 1). MS m/z: 396 (M+1 for free base). Anal. Calcd for C18H17Cl3N4.HCl.1.75H2O: C, 46.59; H, 4.67; N, 12.09; Cl, 30.59. Found: C, 46.64; H, 4.60; N, 11.93; Cl, 30.48. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

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

実験手順: Sodium hydroxide (45.42 g, 1.090 mol) was dissolved in water (220 ml), and while cooling with ice, bromine (16.85 ml, 0.327 mol) was dripped therein over a period of 5 minutes. After stirring the reaction solution at 0° C. for 15 minutes, a dioxane (220 ml) solution of 2′,3′,4′-trichloroacetophenone (24.40 g, 0.109 mol) was dripped therein at 0° C. over a period of 30 minutes. After stirring at room temperature for 14 hours, water (350 ml) was added and then washed with dichloromethane (350 ml). The aqueous layer obtained was gradually made acidic with concentrated hydrochloric acid while cooling with ice and the resulting crystals were filtered out. After washing the filtered-out crystals with water, the water was removed by azeotropic distillation with toluene. 22.33 g (91%) of the title compound was thereby obtained as a pale yellow powder. at 0° C. over a period of 30 minutes After stirring at room temperature for 14 hours washed with dichloromethane (350 ml) The aqueous layer obtained while cooling with ice the resulting crystals were filtered out After washing the filtered-out crystals with water the water was removed by azeotropic distillation with toluene

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

実験手順: Sodium hydroxide (45.42 g, 1.090 mol) was dissolved in water (220 ml), and while cooling with ice, bromine (16.85 ml, 0.327 mol) was dripped therein over a period of 5 minutes. After stirring the reaction solution at 0° C. for 15 minutes, a dioxane (220 ml) solution of 2′,3′,4′-trichloroacetophenone (24.40 g, 0.109 mol) was dripped therein at 0° C. over a period of 30 minutes. After stirring at room temperature for 14 hours, water (350 ml) was added and then washed with dichloromethane (350 ml). The aqueous layer obtained was gradually made acidic with concentrated hydrochloric acid while cooling with ice and the resulting crystals were filtered out. After washing the filtered-out crystals with water, the water was removed by azeotropic distillation with toluene. 22.33 g (91%) of the title compound was thereby obtained as a pale yellow powder. at 0° C. over a period of 30 minutes After stirring at room temperature for 14 hours washed with dichloromethane (350 ml) The aqueous layer obtained while cooling with ice the resulting crystals were filtered out After washing the filtered-out crystals with water the water was removed by azeotropic distillation with toluene

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

実験手順: A mixture of 2',3',4'-trichloroacetophenone (21.4 g, 0.0958 mole), anhydrous sodium acetate (8.0 g), and n-hexane (50 ml) was heated under reflux while treated with a solution of bromine (15.3 g, 0.096 mole) in 25 ml of n-hexane in five portions, decolorizing before each new addition. The mixture was then filtered while hot and the insoluble residue was triturated twice with 50 ml of boiling n-hexane. Enough additional n-hexane was added to the combined filtrates to avoid oiling out of product at 40°. The solution was then seeded and cooled at -10° for 18 hours. Product was collected and air dried to give 17.9 g (62%), mp 44°-46°. was heated under reflux decolorizing before each new addition The mixture was then filtered while hot and the insoluble residue was triturated twice with 50 ml of boiling n-hexane Enough additional n-hexane was added to the combined filtrates to avoid oiling out of product at 40° cooled at -10° for 18 hours Product was collected air dried to give 17.9 g (62%), mp 44°-46°

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

実験手順: A mixture of 2',3',4'-trichloroacetophenone (21.4 g, 0.0958 mole), anhydrous sodium acetate (8.0 g), and n-hexane (50 ml) was heated under reflux while treated with a solution of bromine (15.3 g, 0.096 mole) in 25 ml of n-hexane in five portions, decolorizing before each new addition. The mixture was then filtered while hot and the insoluble residue was triturated twice with 50 ml of boiling n-hexane. Enough additional n-hexane was added to the combined filtrates to avoid oiling out of product at 40°. The solution was then seeded and cooled at -10° for 18 hours. Product was collected and air dried to give 17.9 g (62%), mp 44°-46°. was heated under reflux decolorizing before each new addition The mixture was then filtered while hot and the insoluble residue was triturated twice with 50 ml of boiling n-hexane Enough additional n-hexane was added to the combined filtrates to avoid oiling out of product at 40° cooled at -10° for 18 hours Product was collected air dried to give 17.9 g (62%), mp 44°-46°

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In methanol (284 ml)is suspended 2',3',4'-trichloroacetophenone (94.7 g), and thereto is added sodium borohydride (7.6 g) at 15° C.-25° C. The mixture is stirred at 25° C. for two hours, and evaporated to remove the methanol. To the residue is added 2N hydrochloric acid (110 ml), and the mixture is extracted with ethyl acetate. The organic layer is washed with water, dried, and evaporated to remove the solvent to give crude 1-(2,3,4-trichlorophenyl)ethanol (95 g). evaporated to remove the methanol To the residue is added 2N hydrochloric acid (110 ml) the mixture is extracted with ethyl acetate The organic layer is washed with water dried evaporated to remove the solvent

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In methanol (284 ml)is suspended 2',3',4'-trichloroacetophenone (94.7 g), and thereto is added sodium borohydride (7.6 g) at 15° C.-25° C. The mixture is stirred at 25° C. for two hours, and evaporated to remove the methanol. To the residue is added 2N hydrochloric acid (110 ml), and the mixture is extracted with ethyl acetate. The organic layer is washed with water, dried, and evaporated to remove the solvent to give crude 1-(2,3,4-trichlorophenyl)ethanol (95 g). evaporated to remove the methanol To the residue is added 2N hydrochloric acid (110 ml) the mixture is extracted with ethyl acetate The organic layer is washed with water dried evaporated to remove the solvent

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In methanol (284 ml) is suspended 2',3',4'-trichloroacetophenone (94.7 g), and thereto is added sodium borohydride (7.6 g) at 15° C.-25° C. The mixture is stirred at 25° C. for two hours, and evaporated to remove the methanol. To the residue is added 2N hydrochloric acid (110 ml), and the mixture is extracted with ethyl acetate. The organic layer is washed with water, dried, and evaporated to remove the solvent to give crude 1-(2,3,4-trichlorophenyl)ethanol (95 g). evaporated to remove the methanol To the residue is added 2N hydrochloric acid (110 ml) the mixture is extracted with ethyl acetate The organic layer is washed with water dried evaporated to remove the solvent

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

実験手順: Using the method described in Example 30 by employing [1-(2,3,4-trichlorophenyl]vinyl]pyrrolidine (freshly prepared before use from 2′,3′,4′-trichloro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.00 g, 3.64 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (0.80 g, 3.64 mmol), N,N-diisopropylethylamine (0.6 mL, 3.64 mmol), piperidine (0.6 mL, 5.80 mmol), NEt3 (0.7 mL) and SnCl2 (11 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 125 mg (9%) of 2-methyl-4-piperidyl-6-(2,3,4-trichlorophenyl)pyrrolo[3,2-d]pyrimidine as a brown colored oil. This material (125 mg, 0.32 mmol) was dissolved in 5:1 EtOAc/MeOH (15 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.40 mL, 0.40 mmol). The solution was left to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 55 mg (4%) of the title compound as beige colored needles. Mp: 264-266° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.71 (br s, 6), 2.58 (s, 3), 4.03 (s, 4), 6.78 (s, 1), 7.71 (d, 2, J=8.4), 7.88 (d, 2, J=8.5), 12.40 (s, 1), 14.39 (s, 1). MS m/z: 396 (M+1 for free base). Anal. Calcd for C18H17Cl3N4.HCl.1.75H2O: C, 46.59; H, 4.67; N, 12.09; Cl, 30.59. Found: C, 46.64; H, 4.60; N, 11.93; Cl, 30.48. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

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

実験手順: Using the method described in Example 30 by employing [1-(2,3,4-trichlorophenyl]vinyl]pyrrolidine (freshly prepared before use from 2′,3′,4′-trichloro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.00 g, 3.64 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (0.80 g, 3.64 mmol), N,N-diisopropylethylamine (0.6 mL, 3.64 mmol), piperidine (0.6 mL, 5.80 mmol), NEt3 (0.7 mL) and SnCl2 (11 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 125 mg (9%) of 2-methyl-4-piperidyl-6-(2,3,4-trichlorophenyl)pyrrolo[3,2-d]pyrimidine as a brown colored oil. This material (125 mg, 0.32 mmol) was dissolved in 5:1 EtOAc/MeOH (15 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.40 mL, 0.40 mmol). The solution was left to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 55 mg (4%) of the title compound as beige colored needles. Mp: 264-266° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.71 (br s, 6), 2.58 (s, 3), 4.03 (s, 4), 6.78 (s, 1), 7.71 (d, 2, J=8.4), 7.88 (d, 2, J=8.5), 12.40 (s, 1), 14.39 (s, 1). MS m/z: 396 (M+1 for free base). Anal. Calcd for C18H17Cl3N4.HCl.1.75H2O: C, 46.59; H, 4.67; N, 12.09; Cl, 30.59. Found: C, 46.64; H, 4.60; N, 11.93; Cl, 30.48. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant