tert-butyl N-(3-chloropropyl)-N-methylcarbamate

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:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Suspend 1.7 g (7.8 mmol) of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one in 35 ml of DMF and then add 374 mg (9.35 mmol, 1.2 equivalents) of sodium hydride (60% suspension in oil). A clear pale yellow solution is obtained, which is stirred for one hour at 25° C. 1.94 g (9.35 mmol, 1.2 equivalent) of tert-butyl (3-chloropropyl)methylcarbamate dissolved in 10 ml of DMF are then added dropwise. The whole is heated at 50° C. overnight and then the solvent is evaporated to dryness. The residue is taken up in water and extracted with dichloromethane. The organic phase is dried over MgSO4, filtered and then evaporated to dryness. 4.2 g of an oil is obtained which is purified by flash chromatography on 200 g of silica (eluant=dichloromethane/ethyl acetate:80/20). 2.3 g of the expected product are obtained in the form of a colourless oil. A clear pale yellow solution is obtained are then added dropwise The whole is heated at 50° C. overnight the solvent is evaporated to dryness extracted with dichloromethane The organic phase is dried over MgSO4 filtered evaporated to dryness

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

実験手順: N-tert-Butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (280 mg, 528 μmol), tert-butyl 3-chloropropyl(methyl)carbamate (110 mg, 528 μmol) and cesium carbonate (516 mg, 1.58 mmol) in dimethylformamide (4 mL) were heated in a microwave at 100° C. for 30 min. The mixture was partitioned between ethyl acetate and water, then the organic phase washed with water 3 times, dried, filtered and concentrated. The crude residue was used in the next step without purification. MS (M+H)+=702. The mixture was partitioned between ethyl acetate and water the organic phase washed with water 3 times dried filtered concentrated The crude residue was used in the next step without purification

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

実験手順: N-tert-Butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (280 mg, 528 μmol), tert-butyl 3-chloropropyl(methyl)carbamate (110 mg, 528 μmol) and cesium carbonate (516 mg, 1.58 mmol) in dimethylformamide (4 mL) were heated in a microwave at 100° C. for 30 min. The mixture was partitioned between ethyl acetate and water, then the organic phase washed with water 3 times, dried, filtered and concentrated. The crude residue was used in the next step without purification. MS (M+H)+=702. The mixture was partitioned between ethyl acetate and water the organic phase washed with water 3 times dried filtered concentrated The crude residue was used in the next step without purification

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

実験手順: Suspend 1.7 g (7.8 mmol) of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one in 35 ml of DMF and then add 374 mg (9.35 mmol, 1.2 equivalents) of sodium hydride (60% suspension in oil). A clear pale yellow solution is obtained, which is stirred for one hour at 25° C. 1.94 g (9.35 mmol, 1.2 equivalent) of tert-butyl (3-chloropropyl)methylcarbamate dissolved in 10 ml of DMF are then added dropwise. The whole is heated at 50° C. overnight and then the solvent is evaporated to dryness. The residue is taken up in water and extracted with dichloromethane. The organic phase is dried over MgSO4, filtered and then evaporated to dryness. 4.2 g of an oil is obtained which is purified by flash chromatography on 200 g of silica (eluant=dichloromethane/ethyl acetate:80/20). 2.3 g of the expected product are obtained in the form of a colourless oil. A clear pale yellow solution is obtained are then added dropwise The whole is heated at 50° C. overnight the solvent is evaporated to dryness extracted with dichloromethane The organic phase is dried over MgSO4 filtered evaporated to dryness

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

実験手順: N-tert-Butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (280 mg, 528 μmol), tert-butyl 3-chloropropyl(methyl)carbamate (110 mg, 528 μmol) and cesium carbonate (516 mg, 1.58 mmol) in dimethylformamide (4 mL) were heated in a microwave at 100° C. for 30 min. The mixture was partitioned between ethyl acetate and water, then the organic phase washed with water 3 times, dried, filtered and concentrated. The crude residue was used in the next step without purification. MS (M+H)+=702. The mixture was partitioned between ethyl acetate and water the organic phase washed with water 3 times dried filtered concentrated The crude residue was used in the next step without purification

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (3-Chloro-propyl)-methyl-carbamic acid tert-butyl ester (2.00 g 9.629 mmol) is solubilised in DMF (20 ml) and polystyrene bound DIPEA added, and after a few minutes removed. This solution is then added to a mixture of hydroxy-diphenyl-acetic acid (R)-(1-aza-bicyclo [2.2.2]oct-3-yl) ester (2.1634 g 6.419 mmol) and 200 mg of K2CO3, followed by the addition of sodium iodide (10 mg) and heating at 60° C. for 2 days. 2.5 g Merrifield resin and 100 mg K2CO3 is then added to the mixture and heating resumed at 40° C. for 12 hours. The resin is then removed, and the mixture purified by gradient C18 column chromatography to give the title product. added after a few minutes removed heating The resin is then removed the mixture purified by gradient C18 column chromatography

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

実験手順: Suspend 1.7 g (7.8 mmol) of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one in 35 ml of DMF and then add 374 mg (9.35 mmol, 1.2 equivalents) of sodium hydride (60% suspension in oil). A clear pale yellow solution is obtained, which is stirred for one hour at 25° C. 1.94 g (9.35 mmol, 1.2 equivalent) of tert-butyl (3-chloropropyl)methylcarbamate dissolved in 10 ml of DMF are then added dropwise. The whole is heated at 50° C. overnight and then the solvent is evaporated to dryness. The residue is taken up in water and extracted with dichloromethane. The organic phase is dried over MgSO4, filtered and then evaporated to dryness. 4.2 g of an oil is obtained which is purified by flash chromatography on 200 g of silica (eluant=dichloromethane/ethyl acetate:80/20). 2.3 g of the expected product are obtained in the form of a colourless oil. A clear pale yellow solution is obtained are then added dropwise The whole is heated at 50° C. overnight the solvent is evaporated to dryness extracted with dichloromethane The organic phase is dried over MgSO4 filtered evaporated to dryness

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

実験手順: N-tert-Butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (280 mg, 528 μmol), tert-butyl 3-chloropropyl(methyl)carbamate (110 mg, 528 μmol) and cesium carbonate (516 mg, 1.58 mmol) in dimethylformamide (4 mL) were heated in a microwave at 100° C. for 30 min. The mixture was partitioned between ethyl acetate and water, then the organic phase washed with water 3 times, dried, filtered and concentrated. The crude residue was used in the next step without purification. MS (M+H)+=702. The mixture was partitioned between ethyl acetate and water the organic phase washed with water 3 times dried filtered concentrated The crude residue was used in the next step without purification