1-tert-butyl-4-(isothiocyanatomethyl)benzene

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: A suspension of Benzyl N-{1-Methyl-1-[4-(methylsulfonylamino)phenyl]ethyl}carbamate (21-1, 0.5 mmol) and 5% palladium on carbon (100 mg) in MeOH (10 mL) was hydrogenated under a rubber balloon of hydrogen for 1 h. After the solvent was evaporated by rotary evaporator, the residue was dissolved in DMF (5 mL) and treated with 4-t-butylbenzyl isothiocyanate (0.5 mmol). After being stirred overnight, the mixture went to aqueous work-up and the residue was purified by column chromatography on silica gel with EtOAc:hexanes as eluant to afford N-(4-t-Butylbenzyl)-N′-{1-methyl-1-[4-(methylsulfonylamino)phenyl]ethyl}thiourea (21-7, CHK-593) After the solvent was evaporated by rotary evaporator the residue was dissolved in DMF (5 mL) the residue was purified by column chromatography on silica gel with EtOAc

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

Procedure: 3,5-dimethylpyrazol-1-methanol 33-3 (200 mg) and sodium hydride (42 mg) were dissolved in anhydrous tetrahydrofuran (20 ml) and the solution was stirred for 1 hour. To the solution was added 4-t-butylbenzylisothiocyanate (330 mg) and the mixture was stirred at room temperature for 12 hours. The resulting mixture was filtered under reduced pressure and the solvent was removed therefrom. The residue was purified by column-chromatography (ethyl acetate/hexane=1/2) to yield the compound 33-4 (253 mg, 48%) as a solid. the mixture was stirred at room temperature for 12 hours The resulting mixture was filtered under reduced pressure the solvent was removed The residue was purified by column-chromatography (ethyl acetate/hexane=1/2)

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

Procedure: (1-methyl-1H-pyrrol-2-yl)methylamine (65 mg) and 4-t-butylbenzylisothiocyanate (120 mg) were dissolved in ethyl acetate (30 ml) and the solution was stirred for 12 hours. After the completion of the reaction, the resulting mixture was purified by column-chromatography (ethyl acetate/hexane=1/3) to yield the compound 17-2 (140 mg, 75%) After the completion of the reaction the resulting mixture was purified by column-chromatography (ethyl acetate/hexane=1/3)

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

Procedure: (1H-pyrrol-2-yl)methylamine hydrochloride (60 mg) prepared according to the same procedure as described in Step 2 was dissolved in dichloromethane (2 ml) and to the solution was added 4-t-butylbenzylisothiocyanate (155 mg), followed by stirring at room temperature for 1 hour. The resulting mixture was concentrated under reduced pressure and the obtained residue was column-chromatographed (ethyl acetate/hexane=1/3) to yield the compound 17-1 (120 mg, 65%). The resulting mixture was concentrated under reduced pressure the obtained residue was column-chromatographed (ethyl acetate/hexane=1/3)

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

Procedure: 2-aminopyridine (86 mg) was dissolved in acetonitrile (10 ml) and to the solution were added 4-t-butylbenzylisothiocyanate (190 mg) and triethylamine (140 μl), followed by refluxing for 27 hours. The resulting mixture was extracted with water and dichloromethane, dried, concentrated under reduced pressure, and then crystallized (dichloromethane/petroleum ether) to yield the compound (90 mg, 33%) as a white solid. by refluxing for 27 hours The resulting mixture was extracted with water and dichloromethane dried concentrated under reduced pressure crystallized (dichloromethane/petroleum ether)

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

Procedure: 2-aminopyridine (86 mg) was dissolved in acetonitrile (10 ml) and to the solution were added 4-t-butylbenzylisothiocyanate (190 mg) and triethylamine (140 μl), followed by refluxing for 27 hours. The resulting mixture was extracted with water and dichloromethane, dried, concentrated under reduced pressure, and then crystallized (dichloromethane/petroleum ether) to yield the compound (90 mg, 33%) as a white solid. by refluxing for 27 hours The resulting mixture was extracted with water and dichloromethane dried concentrated under reduced pressure crystallized (dichloromethane/petroleum ether)

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

Procedure: Furan-2-ylmethylamine (0.58 g) was dissolved in dichloromethane (50 ml) and to the solution was added 4-t-butylbenzylisothiocyanate (1.23 g), followed by stirring at room temperature for 8 hours. Then, the resulting mixture was diluted with ethyl acetate, washed with water, dried, and concentrated under reduced pressure. The residue was purified by column-chromatography (dichloromethane) to yield the compound 16-2 (1.57 g, 87%) as a liquid. washed with water dried concentrated under reduced pressure The residue was purified by column-chromatography (dichloromethane)

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

Procedure: 2-(2-thiomorpholin-4-ylethyl)isoindol-1,3-dione 15-1 (2.76 g) was dissolved in a mixture of methanol (20 ml) and tetrahydrofuran (20 ml) and to the solution was added dropwise hydrazine hydrate (550 mg), followed by stirring for 21 hours. To the obtained solution was added 2 N aqueous hydrochloric acid solution (6 ml), and the mixture was stirred for 3 hours and then concentrated under reduced pressure. To the concentrate was added water (15 ml) and the undissolved material was filtered off. The filtrate was concentrated to obtain reaction mixture (1.62 g) as a solid. The obtained mixture (150 mg) was dissolved in dimethylformamide (5 ml) and to the solution was added 4-t-butylbenzylisothiocyanate (210 mg) and a small amount of triethylamine, followed by stirring at room temperature for 23 hours. The resulting mixture was diluted with dichloromethane, washed with water, and concentrated under reduced pressure. The residue was purified by column-chromatography (hexane/ethyl acetate=1/3) to the compound 15-3 (0.12 g) as a white solid. the mixture was stirred for 3 hours concentrated under reduced pressure To the concentrate was added water (15 ml) the undissolved material was filtered off The filtrate was concentrated to obtain by stirring at room temperature for 23 hours washed with water concentrated under reduced pressure The residue was purified by column-chromatography (hexane/ethyl acetate=1/3) to the compound 15-3 (0.12 g) as a white solid