phenyl N-methylcarbamate

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: (R)-2-(4-(Cyclopropylsulfonyl)phenyl)-N-(5-fluorothiazol-2-yl)-3-((S)-pyrrolidin-3-yl)propanamide (500 mg, 1.05 mmol) was dissolved in tetrahydrofuran (40 mL), and thereafter, phenyl N-methylcarbamate (636 mg, 4.21 mmol) and an aqueous solution of sodium hydroxide (2 M, 2 mL) were added to the above obtained solution under ice-cold condition. The obtained mixture was stirred for 1.5 hours. Thereafter, water was added to the reaction solution, and the mixed solution was then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and was then concentrated in vacuo. The obtained residue was purified by silica gel chromatography (chloroform/methanol=1%→15%) to obtain the captioned compound (377 mg, 75%) in the form of a white solid. the mixed solution was then extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate was then concentrated in vacuo The obtained residue was purified by silica gel chromatography (chloroform/methanol=1%→15%)

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

Procedure: (R)-2-(4-(Cyclopropylsulfonyl)phenyl)-N-(5-fluorothiazol-2-yl)-3-((S)-pyrrolidin-3-yl)propanamide (500 mg, 1.05 mmol) was dissolved in tetrahydrofuran (40 mL), and thereafter, phenyl N-methylcarbamate (636 mg, 4.21 mmol) and an aqueous solution of sodium hydroxide (2 M, 2 mL) were added to the above obtained solution under ice-cold condition. The obtained mixture was stirred for 1.5 hours. Thereafter, water was added to the reaction solution, and the mixed solution was then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and was then concentrated in vacuo. The obtained residue was purified by silica gel chromatography (chloroform/methanol=1%→15%) to obtain the captioned compound (377 mg, 75%) in the form of a white solid. the mixed solution was then extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate was then concentrated in vacuo The obtained residue was purified by silica gel chromatography (chloroform/methanol=1%→15%)

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

Procedure: 15.1 g. of phenyl N-methylcarbamate, 9.3 g. of aniline and 5.4 g. of the tetraethylammonium salt of 2-hydroxy-5-nitro-pyridine are refluxed in 200 ml. of ethanol for 5 hours. The reaction solution is concentrated, and the residue is dissolved in 100 ml. of chloroform, washed successively with 50 ml. of 1N sodium carbonate, 50 ml. of 1N hydrochloric acid and 100 ml. of water, and dried. By concentrating to dryness and recrystallizing from 120 ml. of ethanol, crystals of N-methyl-N-phenylurea having a m.p. of 150° - 151° C. are obtained in 91% yield. The reaction solution is concentrated the residue is dissolved in 100 ml of chloroform, washed successively with 50 ml of water, and dried By concentrating to dryness recrystallizing from 120 ml

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

Procedure: 15.1 g. of phenyl N-methylcarbamate, 9.3 g. of aniline and 5.4 g. of tetraethylammonium salt of 2-hydroxy-5-nitro-pyridine are refluxed in 200 ml. of ethanol for 5 hours. The reaction solution is concentrated, and the residue is dissolved in 100 ml. of chloroform, washed successively with 50 ml. of 1N sodium carbonate, 50 ml. of 1N hydrochloric acid and 100 ml. of water, and dried. By concentrating to dryness and recrystallizing from 120 ml. of ethanol, crystals of N-methyl-N-phenylurea having a m.p. of 150° - 151° C. are obtained in 91 percent yield. The reaction solution is concentrated the residue is dissolved in 100 ml of chloroform, washed successively with 50 ml of water, and dried By concentrating to dryness recrystallizing from 120 ml

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

Procedure: 15.1 g. of phenyl N-methylcarbamate, 9.3 g. of aniline and 5.4 g. of tetraethylammonium salt of 2-hydroxy-5-nitro-pyridine are refluxed in 200 ml. of ethanol for 5 hours. The reaction solution is concentrated, and the residue is dissolved in 100 ml. of chloroform, washed successively with 50 ml. of 1N sodium carbonate, 50 ml. of 1N hydrochloric acid and 100 ml. of water, and dried. By concentrating to dryness and recrystallizing from 120 ml. of ethanol, crystals of N-methyl-N-phenylurea having a m.p. of 150° - 151° C. are obtained in 91 percent yield. The reaction solution is concentrated the residue is dissolved in 100 ml of chloroform, washed successively with 50 ml of water, and dried By concentrating to dryness recrystallizing from 120 ml

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: Sodium hydride (60% in oil, 228 mg, 5.7 mmol) was gradually added to a N,N-dimethylformamide (0.5 ml) solution of 5-nitroindole (0.841 g, 5.19 mmol) while stirring at room temperature; phenyl N-methylcarbamate (1.02 g, 6.74 mmol) was added thereto; and the reaction mixture was stirred overnight. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was washed with water and brine, dried over anhydrous sodium sulfate. This was concentrated under reduced pressure; and the residue was purified by silica gel column chromatography (hexane-ethyl acetate, sequentially ethyl acetate) to yield the title compound (600 mg). and the reaction mixture was stirred overnight The reaction mixture was partitioned between ethyl acetate and water and the organic layer was washed with water and brine dried over anhydrous sodium sulfate This was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane-ethyl acetate, sequentially ethyl acetate)

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

Procedure: Phenyl N-methylcarbamate (350 mg, Production example 2-1) was added to a solution of 4-(3-methyl-1H-5-indolyl)oxy-2-pyridinamine (500 mg), sodium hydride (93 mg) and N,N-dimethylformamide (5 ml) at room temperature; and the reaction mixture was stirred for 2 hours and 45 minutes. Water was added to the reaction mixture; extraction was performed with ethyl acetate; and purification was performed by NH-silica gel column chromatography (Fuji Silysia, hexane:ethyl acetate=1:2, sequentially, ethyl acetate) to yield the title compound as a pale yellow amorphous solid (365 mg). extraction and purification