phenyl N-cyclopropylcarbamate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [4-(4-Amino-3-fluorophenoxy)-7-methoxyquinolin-6-yl]carbamic acid benzyl ester (100 mg) and cyclopropylcarbamic acid phenyl ester (64 mg) were heated and stirred in dimethylsulfoxide (0.7 ml) at 85° C. for 5 hours and 40 minutes, in the same manner as Example 224, to obtain the title compound (11 mg) as a solid.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: After adding 28 mg of sodium hydride (60% in oil) to a solution of 150 mg of 5-[(2-amino-4-pyridyl)oxy]-1H-indole in dimethylformamide at room temperature and stirring for 5 minutes, the mixture was cooled to 0° C., 124 mg of phenyl N-cyclopropylcarbamate was added and the mixture was further stirred for 30 minutes. Water was added, extraction was performed with ethyl acetate, the organic layer was washed 3 times with water and once with ammonium chloride water, and then silica gel was added and the solvent was distilled off under reduced pressure. The silica gel was charged into a dry column packed with silica gel and purification was performed by column chromatography (hexane:ethyl acetate=1:1, followed by ethyl acetate), to obtain 2.4 g of a colorless powder. the mixture was further stirred for 30 minutes extraction the organic layer was washed 3 times with water once with ammonium chloride water, and then silica gel was added the solvent was distilled off under reduced pressure The silica gel was charged into a dry column packed with silica gel and purification

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenyl N-cyclopropylcarbamate (120 mg) was added to a solution of 260 mg of 5-[(2-{[4-(4-hydroxypiperidino)butanoyl]amino}-4-pyridyl)oxy]indole, 53 mg of sodium hydride (60% in oil) and 5 ml of dimethylformamide while stirring at room temperature. After stirring for 10 minutes, water was added and extraction was performed with ethyl acetate. NH type silica gel was added to the ethyl acetate layer, the solvent was distilled off under reduced pressure and the reaction product was adsorbed onto the silica gel. The silica gel was charged into a dry column packed with NH type silica gel, and purification was performed by column chromatography (chloroform:methanol=30:1). The solvent was distilled off under reduced pressure, and the residue was dissolved in ethyl acetate and washed twice with 1N aqueous sodium hydroxide. After drying over sodium sulfate, the solvent was distilled off under reduced pressure to obtain 20 mg of the target substance as a white powder. After stirring for 10 minutes extraction NH type silica gel was added to the ethyl acetate layer the solvent was distilled off under reduced pressure The silica gel was charged into a dry column packed with NH type silica gel, and purification The solvent was distilled off under reduced pressure the residue was dissolved in ethyl acetate washed twice with 1N aqueous sodium hydroxide After drying over sodium sulfate the solvent was distilled off under reduced pressure to obtain 20 mg of the target substance as a white powder

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: After adding 30 mg of phenyl cyclopropylcarbamate and 0.5 ml of dimethylsulfoxide to 40 mg of 4-(6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenylamine, the mixture was stirred at 80° C. for 4 hours. The mixture was returned to room temperature, water was added, liquid separation and extraction were performed with ethyl acetate, and the solid obtained by concentration to dryness was washed with ether to obtain 6 mg of the title compound. was returned to room temperature liquid separation and extraction the solid obtained by concentration to dryness was washed with ether

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: After dissolving the 2-chloro-4-[6-[4-(3-diethylaminopropoxy)phenyl]-7-(2-trimethylsilanylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]phenylamine synthesized in Production Example 160-2 in 0.6 ml of dimethylsulfoxide, 23 mg of phenyl cyclopropylcarbamate was added and the mixture was stirred at 80° C. for 1.5 hours. After further adding 75 mg of phenyl cyclopropylcarbamate and stirring at 100° C. for 5 hours, 70 mg of the same reagent was added prior to stirring overnight. The mixture was then returned to room temperature, water was added, and liquid separation and extraction were performed with an ethyl acetate:tetrahydrofuran (5:1) mixed solvent. The organic layer was dried over sodium sulfate, concentrated and subjected to NH silica gel column chromatography (hexane-ethyl acetate) to obtain 18 mg of the title compound. stirring at 100° C. for 5 hours to stirring overnight was then returned to room temperature liquid separation and extraction mixed solvent The organic layer was dried over sodium sulfate concentrated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-(2-tetrahydropyranyloxy)-2-[7-(5-(4-(5-oxazolyl)phenyl)-2-thienyl)-1,1-dioxoperhydro-1,4-thiazepin-7-yl]acetamide (100 mg) in N,N-dimethylformamide (3 ml) was added triethylamine (57 mg) and cyclopropylaminocarbonyloxybenzene (40 mg) and the reaction mixture was heated at 50° C. for 4 hours. The mixture was added ethyl acetate and the solution was washed with successively water, a 5% aqueous citric acid-solution, a satuated aqueous sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel 60 (2% methanol-chloroform) to give N-(2-tetrahydropyranyloxy)-2-[4-cyclopropylaminocarbonyl-7-(5-(4-(5-oxazolyl)phenyl)-2-thienyl)-1,1-dioxoperhydro-1,4-thiazepin-7-yl]acetamide (65 mg) as a pale yellow powder. the solution was washed with successively water a 5% aqueous citric acid-solution, a satuated aqueous sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate concentrated in vacuo The residue was purified by column chromatography on silica gel 60 (2% methanol-chloroform)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of cyclopropylamine (500 mg) in chloroform (5 ml) were added pyridine (1.04 mg) and a solution of phenyl chloroformate (1.65 g) in chloroform (2 ml) 0° C. and the reaction mixture was stirred at ambient temperature for 0.5 hour. To the mixture was added ethyl acetate and the solution was washed successively with water, a 5% aqueous citric acid solution, a saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give cyclopropylaminocarbonyloxybenzene (1.6 g) as a pale yellow powder. the solution was washed successively with water a 5% aqueous citric acid solution, a saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [4-(4-Amino-3-fluorophenoxy)-7-methoxyquinolin-6-yl]carbamic acid benzyl ester (100 mg) and cyclopropylcarbamic acid phenyl ester (64 mg) were heated and stirred in dimethylsulfoxide (0.7 ml) at 85° C. for 5 hours and 40 minutes, in the same manner as Example 224, to obtain the title compound (11 mg) as a solid.