(4-iodophenyl)-morpholin-4-ylmethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A mixture of 4-[(4-iodophenyl)carbonyl]morpholine (1.90 g, 6.0 mmol), 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (1.14 g, 6.0 mmol), copper (I) oxide (10 mol %, 0.6 mmol, 86 mg), N,N-dimethylglycine (20 mol %, 1.2 mmol, 124 mg), and cesium carbonate (12.0 mmol, 3.91 g) in dimethylsulfoxide (16 ml) was stirred in an oilbath heated at 130° C. for 24 h under argon and then allowed to cool to room temperature. The reaction mixture was partitioned between dichloromethane (30 ml) and water (30 ml). The organic layer was separated and dried over sodium sulphate. The solvent was removed by rotary evaporation to give a dark brown residue that was added to a 20 g isolute pre-packed silica column and eluted from 0-50% ethyl acetate in petroleum ether to give the title compound as a brown gum (1.86 g, 82%). to cool to room temperature The reaction mixture was partitioned between dichloromethane (30 ml) and water (30 ml) The organic layer was separated dried over sodium sulphate The solvent was removed by rotary evaporation to give a dark brown residue that was added to a 20 g isolute pre-packed silica column eluted from 0-50% ethyl acetate in petroleum ether

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

実験手順: A solution of morpholine (653 mg, 7.5 mmol) in dichloromethane (40 ml) was cooled in an ice/methanol bath and then treated with stirring under argon with triethylamine (7.5 mmol, 1.05 ml) followed by the portionwise addition of 4-iodobenzoyl chloride (2.0 g, 7.5 mmol). The reaction mix was allowed to stir at room temperature for 0.5 h before the solution was washed with water (2×20 ml). The organic layer was dried over sodium sulphate and evaporated under reduced pressure to give the title compound as a yellow solid (2.4 g, 100%). treated The reaction mix was washed with water (2×20 ml) The organic layer was dried over sodium sulphate evaporated under reduced pressure

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

実験手順: 4-Imidazo[1,2-α]pyridin-3-yl-pyrimidin-2-ylamine(Bioorganic & Medicinal Chemistry Letters 2004, 14(9), 2245-2248) (0.20 g, 0.95 mmol), palladium acetate (9 mg, 0.038 mmol), Xanthphos (33 mg, 0.057 mmol), caesium carbonate (0.46 g, 1.4 mmol) and (4-iodo-phenyl)-morpholin-4-yl-methanone (Method 16a in WO 05/044814) (330 mg, 1.05 mmol) were added to dioxane (7 ml) under a inert atmosphere and heated at reflux for 6 hours. Purification on silica using 0-10% MeOH in DCM as eluent gave the title compound as a colourless foam. Further purification was achieved using RPHPLC to give a colourless foam (239 mg, 63%); 1H NMR (400.132 MHz) 10.13 (d, 1H), 9.89 (s, 1H), 8.64 (s, 1H), 8.48 (d, 1H), 7.85 (d, 2H), 7.79 (d, 1H), 7.52 (t, 1H), 7.46 (d, 1H), 7.43 (d, 2H), 7.16 (t, 1H), 3.65-3.60 (m, 4H), 3.58-3.51 (m, 4H); MH+ 401. heated at reflux for 6 hours Purification on silica using 0-10% MeOH in DCM as eluent

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

実験手順: A mixture of 4-[(4-iodophenyl)carbonyl]morpholine (1.90 g, 6.0 mmol), 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (1.14 g, 6.0 mmol), copper (I) oxide (10 mol %, 0.6 mmol, 86 mg), N,N-dimethylglycine (20 mol %, 1.2 mmol, 124 mg), and cesium carbonate (12.0 mmol, 3.91 g) in dimethylsulfoxide (16 ml) was stirred in an oilbath heated at 130° C. for 24 h under argon and then allowed to cool to room temperature. The reaction mixture was partitioned between dichloromethane (30 ml) and water (30 ml). The organic layer was separated and dried over sodium sulphate. The solvent was removed by rotary evaporation to give a dark brown residue that was added to a 20 g isolute pre-packed silica column and eluted from 0-50% ethyl acetate in petroleum ether to give the title compound as a brown gum (1.86 g, 82%). to cool to room temperature The reaction mixture was partitioned between dichloromethane (30 ml) and water (30 ml) The organic layer was separated dried over sodium sulphate The solvent was removed by rotary evaporation to give a dark brown residue that was added to a 20 g isolute pre-packed silica column eluted from 0-50% ethyl acetate in petroleum ether

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

実験手順: A solution of morpholine (653 mg, 7.5 mmol) in dichloromethane (40 ml) was cooled in an ice/methanol bath and then treated with stirring under argon with triethylamine (7.5 mmol, 1.05 ml) followed by the portionwise addition of 4-iodobenzoyl chloride (2.0 g, 7.5 mmol). The reaction mix was allowed to stir at room temperature for 0.5 h before the solution was washed with water (2×20 ml). The organic layer was dried over sodium sulphate and evaporated under reduced pressure to give the title compound as a yellow solid (2.4 g, 100%). treated The reaction mix was washed with water (2×20 ml) The organic layer was dried over sodium sulphate evaporated under reduced pressure

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: 4-Imidazo[1,2-α]pyridin-3-yl-pyrimidin-2-ylamine(Bioorganic & Medicinal Chemistry Letters 2004, 14(9), 2245-2248) (0.20 g, 0.95 mmol), palladium acetate (9 mg, 0.038 mmol), Xanthphos (33 mg, 0.057 mmol), caesium carbonate (0.46 g, 1.4 mmol) and (4-iodo-phenyl)-morpholin-4-yl-methanone (Method 16a in WO 05/044814) (330 mg, 1.05 mmol) were added to dioxane (7 ml) under a inert atmosphere and heated at reflux for 6 hours. Purification on silica using 0-10% MeOH in DCM as eluent gave the title compound as a colourless foam. Further purification was achieved using RPHPLC to give a colourless foam (239 mg, 63%); 1H NMR (400.132 MHz) 10.13 (d, 1H), 9.89 (s, 1H), 8.64 (s, 1H), 8.48 (d, 1H), 7.85 (d, 2H), 7.79 (d, 1H), 7.52 (t, 1H), 7.46 (d, 1H), 7.43 (d, 2H), 7.16 (t, 1H), 3.65-3.60 (m, 4H), 3.58-3.51 (m, 4H); MH+ 401. heated at reflux for 6 hours Purification on silica using 0-10% MeOH in DCM as eluent