(2,6-dichlorophenyl)thiourea

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: 2,6-Dichlorophenylthiourea (3.0 g, 13.6 mmol) was dissolved in 50 mL of dry methanol and dimethyl acetylenedicarboxylate (13.8 mmol, 1.7 mL) was added over a 10-minute period. The mixture was stirred at 25° C. for 40 minutes, then the mixture was heated at 55° C. for 3 hours. The solvent was removed by rotvap, and the crude product was recrystallized from methanol to yield the desired product. the mixture was heated at 55° C. for 3 hours The solvent was removed by rotvap the crude product was recrystallized from methanol

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

実験手順: A solution of 156.9 g. of 1-(2,6-dichlorophenyl)thiourea in 1 1. of chlorobenzene was refluxed for 20 hours and concentrated. The resulting oil was triturated with 1 1. of hot hexane which was filtered. On cooling overnight, 52 g. (36%) of 2,6-dichlorophenylisothiocyanate, m.p. 41°-42° separated. Concentration of the filtrate gave an additional 64.2 g. (44%), m.p. 41°-43° in two crops. Recrystallization of a sample from hexane gave the analytical sample, m.p. 41°-42°. concentrated The resulting oil was triturated with 1 1 of hot hexane which was filtered On cooling overnight (36%) of 2,6-dichlorophenylisothiocyanate, m.p. 41°-42° separated Concentration of the filtrate gave an additional 64.2 g Recrystallization of a sample from hexane gave the analytical sample, m.p. 41°-42°

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

実験手順: To a mixture of 11 g (0.05 mole) of 1-(2,6-dichlorophenyl)thiourea and 10 ml of xylene is added 5 g of t-butylisocyanate (0.05 mole) and the mixture is refluxed for 2 hours. The reaction product is cooled, triturated with heptane and filtered. Recrystallization from 1:1 isopropanol/water results in 1-(2,6-dichlorophenyl)-3-(t-butylcarbamyl)thiourea. the mixture is refluxed for 2 hours The reaction product is cooled triturated with heptane filtered Recrystallization from 1:1 isopropanol/water results in 1-(2,6-dichlorophenyl)-3-(t-butylcarbamyl)thiourea

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

実験手順: A solution of 156.9 g. of 1-(2,6-dichlorophenyl)thiourea in 1 l. of chlorobenzene was refluxed for 20 hours and concentrated. The resulting oil was triturated with 1 l. of hot hexane which was filtered. On cooling overnight, 52 g. (36%) of 2,6-dichlorophenylisothiocyanate, m.p. 41°-42° separated. Concentration of the filtrate gave an additional 64.2 g. (44%), m.p. 41°-43° in two crops. Recrystallization of a sample from hexane gave the analytical sample, m.p. 41°-42°. concentrated The resulting oil was triturated with 1 l of hot hexane which was filtered On cooling overnight (36%) of 2,6-dichlorophenylisothiocyanate, m.p. 41°-42° separated Concentration of the filtrate gave an additional 64.2 g Recrystallization of a sample from hexane gave the analytical sample, m.p. 41°-42°

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

実験手順: To a mixture of 11 g (0.05 mole) of 1-(2,6-dichlorophenyl)thiourea and 10 ml of xylene is added 5 g of t-butylisocyanate (0.05 mole) and the mixture is refluxed for 2 hours. The reaction product is cooled, triturated with heptane and filtered. Recrystallization from 1:1 isopropanol/water results in 1-(2,6-dichlorophenyl)-3-(t-butylcarbamyl)thiourea. the mixture is refluxed for 2 hours The reaction product is cooled triturated with heptane filtered Recrystallization from 1:1 isopropanol/water results in 1-(2,6-dichlorophenyl)-3-(t-butylcarbamyl)thiourea

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

実験手順: A solution of 156.9 g. of 1-(2,6-dichlorophenyl)thiourea in 1 l. of chlorobenzene was refluxed for 20 hours and concentrated. The resulting oil was triturated with 1 l. of hot hexane which was filtered. On cooling overnight, 52 g. (36%) of 2,6-dichlorophenylisothiocyanate, m.p. 41°-42° separated. Concentration of the filtrate gave an additional 64.2 g. (44%), m.p. 41°-43° in two crops. Recrystallization of a sample from hexane gave the analytical sample, m.p. 41°-42°. concentrated The resulting oil was triturated with 1 l of hot hexane which was filtered On cooling overnight (36%) of 2,6-dichlorophenylisothiocyanate, m.p. 41°-42° separated Concentration of the filtrate gave an additional 64.2 g Recrystallization of a sample from hexane gave the analytical sample, m.p. 41°-42°

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

実験手順: Methyl 4-(2-bromoacetyl)-5-methylthiothiophene-2-carboxylate (60 mg, 0.19 mmol) was allowed to react with 2,6-dichlorophenyl thiourea (42 mg) as described in Example 154, step (a) to give 63.1 mg (65% yield) of methyl 4-{2-[(2,6-dichlorophenyl)amino](1,3-thiazol-4-yl)}-5-methylthiothiophene-2-carboxylate hydrobromide. 1H NMR (DMSO-d6, 300 MHz) δ2.59 (s, 3H), 3.8 (s, 3H), 7.15 (s, 1H), 7.36 (m, 1H), 7.61 (m, 2H), 7.97 (s, 1H); Mass Spectrum (ESI) m/z calcd. for C16H12Cl2N2O2S3, 431.38 (M+H), found 431.0, 433.0.

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

実験手順: Methyl 4-(2-bromoacetyl)-5-methylthiothiophene-2-carboxylate (60 mg, 0.19 mmol) was allowed to react with 2,6-dichlorophenyl thiourea (42 mg) as described in Example 154, step (a) to give 63.1 mg (65% yield) of methyl 4-{2-[(2,6-dichlorophenyl)amino](1,3-thiazol-4-yl)}-5-methylthiothiophene-2-carboxylate hydrobromide. 1H NMR (DMSO-d6, 300 MHz) δ2.59 (s, 3H), 3.8 (s, 3H), 7.15 (s, 1H), 7.36 (m, 1H), 7.61 (m, 2H), 7.97 (s, 1H); Mass Spectrum (ESI) m/z calcd. for C16H12Cl2N2O2S3, 431.38 (M+H), found 431.0, 433.0.

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

実験手順: Methyl 4-(2-bromoacetyl)-5-methylthiothiophene-2-carboxylate (60 mg, 0.19 mmol) was allowed to react with 2,6-dichlorophenyl thiourea (42 mg) as described in Example 154, step (a) to give 63.1 mg (65% yield) of methyl 4-{2-[(2,6-dichlorophenyl)amino](1,3-thiazol-4-yl)}-5-methylthiothiophene-2-carboxylate hydrobromide. 1H NMR (DMSO-d6, 300 MHz) δ2.59 (s, 3H), 3.8 (s, 3H), 7.15 (s, 1H), 7.36 (m, 1H), 7.61 (m, 2H), 7.97 (s, 1H); Mass Spectrum (ESI) m/z calcd. for C16H12Cl2N2O2S3, 431.38 (M+H), found 431.0, 433.0.

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 87 mg (1.2 mmol) of (2,6-dichlorophenyl)-thiourea is added to a suspension of 124 mg (0.33 mmol) of 8-(2-bromo-acetyl)-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate in 3.5 mL of ethanol. The mixture is stirred at 90° C. for 6 hours then the mixture is cooled to room temperature. The solvent is evaporated, then the product is purified by preparative LCMS. After drying, 43 mg (26%) of 8-[2-(2,6-dichlorophenylamino)-thiazol-4-yl]-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate is obtained in the form of a beige solid. the mixture is cooled to room temperature The solvent is evaporated the product is purified by preparative LCMS After drying

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

実験手順: A solution of 156.9 g. of 1-(2,6-dichlorophenyl)thiourea in 1 l. of chlorobenzene was refluxed for 20 hours and concentrated. The resulting oil was triturated with 1 l. of hot hexane which was filtered. On cooling overnight, 52 g. (36%) of 2,6-dichlorophenylisothiocyanate, m.p. 41°-42° separated. Concentration of the filtrate gave an additional 64.2 g. (44%), m.p. 41°-43° in two crops. Recrystallization of a sample from hexane gave the analytical sample, m.p. 41°-42°. concentrated The resulting oil was triturated with 1 l of hot hexane which was filtered On cooling overnight (36%) of 2,6-dichlorophenylisothiocyanate, m.p. 41°-42° separated Concentration of the filtrate gave an additional 64.2 g Recrystallization of a sample from hexane gave the analytical sample, m.p. 41°-42°