1-methylsulfanylpropan-2-one

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

Procedure: To a 200 ml volume four-necked flask, 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazine ((12-1)-(11)-39) (6.44 g), tetrahydrofuran (72 ml), and acetic acid (1.65 g) were added under a nitrogen atmosphere. 1-methylsulfanyl-2-propanone (7-0-1) (3.12 g) was added at room temperature, and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added water (30 ml), and extracted with tert-butyl methyl ether. The organic layer was concentrated under reduced pressure to give 7.17 g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfanyl-2-propylidene)hydrazine ((4-4)-(8)-39). extracted with tert-butyl methyl ether The organic layer was concentrated under reduced pressure

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

Procedure: To a 20 ml volume two-necked flask, 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine ((12-2)-(11)-39) (0.50 g), tetrahydrofuran (anhydrous) (9 ml), and 1-methylsulfanyl-2-propanone (7-0-1) (0.23 g) were added and stirred at room temperature for 22 hours under a nitrogen atmosphere. Additional 1-methylsulfanyl-2-propanone (7-0-1) (0.12 g) was added thereto, and the mixture was further stirred at room temperature for 7 hours. Then, the reaction mixture was concentrated under reduced pressure. After the concentration, the residue was subjected to column chromatography (hexane:ethyl acetate=1:1) to gave 0.58 g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine ((4-4)-(1)-39). the mixture was further stirred at room temperature for 7 hours Then, the reaction mixture was concentrated under reduced pressure After the concentration

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

Procedure: To a 200 ml volume four-necked flask, 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazine ((12-1)-(11)-39) (6.44 g), tetrahydrofuran (72 ml), and acetic acid (1.65 g) were added under a nitrogen atmosphere. 1-methylsulfanyl-2-propanone (7-0-1) (3.12 g) was added at room temperature, and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added water (30 ml), and extracted with tert-butyl methyl ether. The organic layer was concentrated under reduced pressure to give 7.17 g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfanyl-2-propylidene)hydrazine ((4-4)-(8)-39). extracted with tert-butyl methyl ether The organic layer was concentrated under reduced pressure

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

Procedure: To a 200 ml volume four-necked flask, 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazine ((12-1)-(11)-39) (6.44 g), tetrahydrofuran (72 ml), and acetic acid (1.65 g) were added under a nitrogen atmosphere. 1-methylsulfanyl-2-propanone (7-0-1) (3.12 g) was added at room temperature, and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added water (30 ml), and extracted with tert-butyl methyl ether. The organic layer was concentrated under reduced pressure to give 7.17 g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfanyl-2-propylidene)hydrazine ((4-4)-(8)-39). extracted with tert-butyl methyl ether The organic layer was concentrated under reduced pressure

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

Procedure: To a 20 ml volume two-necked flask, 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine ((12-2)-(11)-39) (0.50 g), tetrahydrofuran (anhydrous) (9 ml), and 1-methylsulfanyl-2-propanone (7-0-1) (0.23 g) were added and stirred at room temperature for 22 hours under a nitrogen atmosphere. Additional 1-methylsulfanyl-2-propanone (7-0-1) (0.12 g) was added thereto, and the mixture was further stirred at room temperature for 7 hours. Then, the reaction mixture was concentrated under reduced pressure. After the concentration, the residue was subjected to column chromatography (hexane: ethyl acetate=1:1) to gave 0.58 g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine ((4-4)-(1)-39). the mixture was further stirred at room temperature for 7 hours Then, the reaction mixture was concentrated under reduced pressure After the concentration

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

Procedure: A solution of 145 g of 2-bromo-4-fluoro-5-morpholinoaniline in 1 l of methylene chloride and the solution was cooled to a temperature of not higher than -50° C. on a dry ice-acetone bath. At the same temperature as above 60 g of tert-butyl hypochlorite was added dropwise to the solution during which operation the reaction system changed from heterogeneous mixture to homogeneous solution. Then, 67 g of methylthio-2-propanone was added dropwise to the solution and the mixture was reacted at the same temperature as above for 2 hours followed by adding dropwise 80 ml of triethylamine. After completion of addition, the temperature of the mixture was elevated slowly to room temperature. After room temperature was attained 1 l of water was added to separate the methylene chloride layer which then was dried over sodium sulfate and concentrated under reduced pressure to give 150 g of 2-methyl-3-methylthio-5-fluoro-4-morpholino-7-bromoindole. the mixture was reacted at the same temperature as above for 2 hours After completion of addition was elevated slowly to room temperature After room temperature was added to separate the methylene chloride layer which then was dried over sodium sulfate concentrated under reduced pressure

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

Procedure: A solution of 145 g of 2-bromo-4-fluoro-5-morpholinoaniline in 1 l of methylene chloride and the solution was cooled to a temperature of not higher than -50° C. on a dry ice-acetone bath. At the same temperature as above 60 g of tert-butyl hypochlorite was added dropwise to the solution during which operation the reaction system changed from heterogeneous mixture to homogeneous solution. Then, 67 g of methylthio-2-propanone was added dropwise to the solution and the mixture was reacted at the same temperature as above for 2 hours followed by adding dropwise 80 ml of triethylamine. After completion of addition, the temperature of the mixture was elevated slowly to room temperature. After room temperature was attained 1 l of water was added to separate the methylene chloride layer which then was dried over sodium sulfate and concentrated under reduced pressure to give 150 g of 2-methyl-3-methylthio-5-fluoro-4-morpholino-7-bromoindole. the mixture was reacted at the same temperature as above for 2 hours After completion of addition was elevated slowly to room temperature After room temperature was added to separate the methylene chloride layer which then was dried over sodium sulfate concentrated under reduced pressure

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

Procedure: To a 200 ml volume four-necked flask, 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazine ((12-1)-(11)-39) (6.44 g), tetrahydrofuran (72 ml), and acetic acid (1.65 g) were added under a nitrogen atmosphere. 1-methylsulfanyl-2-propanone (7-0-1) (3.12 g) was added at room temperature, and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added water (30 ml), and extracted with tert-butyl methyl ether. The organic layer was concentrated under reduced pressure to give 7.17 g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfanyl-2-propylidene)hydrazine ((4-4)-(8)-39). extracted with tert-butyl methyl ether The organic layer was concentrated under reduced pressure

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

Procedure: To a 200 ml volume four-necked flask, 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazine ((12-1)-(11)-39) (6.44 g), tetrahydrofuran (72 ml), and acetic acid (1.65 g) were added under a nitrogen atmosphere. 1-methylsulfanyl-2-propanone (7-0-1) (3.12 g) was added at room temperature, and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added water (30 ml), and extracted with tert-butyl methyl ether. The organic layer was concentrated under reduced pressure to give 7.17 g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfanyl-2-propylidene)hydrazine ((4-4)-(8)-39). extracted with tert-butyl methyl ether The organic layer was concentrated under reduced pressure

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

Procedure: To a 20 ml volume two-necked flask, 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine ((12-2)-(11)-39) (0.50 g), tetrahydrofuran (anhydrous) (9 ml), and 1-methylsulfanyl-2-propanone (7-0-1) (0.23 g) were added and stirred at room temperature for 22 hours under a nitrogen atmosphere. Additional 1-methylsulfanyl-2-propanone (7-0-1) (0.12 g) was added thereto, and the mixture was further stirred at room temperature for 7 hours. Then, the reaction mixture was concentrated under reduced pressure. After the concentration, the residue was subjected to column chromatography (hexane:ethyl acetate=1:1) to gave 0.58 g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine ((4-4)-(1)-39). the mixture was further stirred at room temperature for 7 hours Then, the reaction mixture was concentrated under reduced pressure After the concentration

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

Procedure: To a 20 ml volume two-necked flask, 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine ((12-2)-(11)-39) (0.50 g), tetrahydrofuran (anhydrous) (9 ml), and 1-methylsulfanyl-2-propanone (7-0-1) (0.23 g) were added and stirred at room temperature for 22 hours under a nitrogen atmosphere. Additional 1-methylsulfanyl-2-propanone (7-0-1) (0.12 g) was added thereto, and the mixture was further stirred at room temperature for 7 hours. Then, the reaction mixture was concentrated under reduced pressure. After the concentration, the residue was subjected to column chromatography (hexane:ethyl acetate=1:1) to gave 0.58 g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine ((4-4)-(1)-39). the mixture was further stirred at room temperature for 7 hours Then, the reaction mixture was concentrated under reduced pressure After the concentration

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using the procedure described in J. Amer. Chem. Soc., 1974, 96 (17) 5495 , 2-chloroaniline (1.27 g, 10 mmole) was dissolved in dichloromethane (35 ml) and cooled to −65° C. To this solution was added dropwise with vigorous stirring, t-butyl hypochlorite (1.08 g, 10 mmole) in dichloromethane (5 ml). After 10 minutes 1-methylsulfanyl-propan-2-one (1.04 g, 10 mmole) dissolved in dichloromethane (5 ml) was added. The mixture was stirred at −65° C. for 1 h more. At this point triethylamine (1.01 g, 10 mmole) dissolved in dichloromethane (5 ml) was added. Upon completion of the addition, the reaction mixture was allowed to reach ambient temperature. Water was added and the layers were separated, the organic layer was dried over magnesium sulfate, filtered and the solvent evaporated to dryness. The residue was purified by column chromatography on silica gel using a mixture of hexane-ethyl acetate (95:5) to elute 7-chloro-2-methyl-3-methylsulfanyl-1H-indole (1.94 g) as an oil. was added was added Upon completion of the addition to reach ambient temperature the layers were separated the organic layer was dried over magnesium sulfate filtered the solvent evaporated to dryness The residue was purified by column chromatography on silica gel using a mixture of hexane-ethyl acetate (95:5) to elute 7-chloro-2-methyl-3-methylsulfanyl-1H-indole (1.94 g) as an oil