2-chloro-4-methylsulfonylaniline

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

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

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloro-4-Methylsulfonylaniline in a 1:1:3 mixture (0.4 M) of Acetic Acid, Hydrochloric Acid, 37% and Water was cooled to 0° C. and slowly treated with a 4 M solution of sodium nitrite in water. The reaction was stirred at 5° C. for 30 minutes then treated dropwise with a 2M solution of potassium iodide in water. The reaction evolved a gas and turned brown. The reaction was stirred 15 minutes at 0° C., 40 minutes at rt and 1 h at 60° C. The brown solid was filtered, dissolved in ethyl acetate and the solution washed with acidified sodium thiosulfate and then brine. The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. During evaporation, a precipitate appeared and was filtered. The mother liquors were evaporated further and 2 more crops were collected. The last mother liquor was transferred with diethyl ether and upon evaporation yields more products. The reaction was stirred 15 minutes at 0° C., 40 minutes at rt and 1 h at 60° C The brown solid was filtered dissolved in ethyl acetate the solution washed with acidified sodium thiosulfate The organic phase was dried over magnesium sulfate concentrated under reduced pressure During evaporation was filtered The mother liquors were evaporated further 2 more crops were collected The last mother liquor was transferred with diethyl ether and upon evaporation yields more products

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloro-4-Methylsulfonylaniline in a 1:1:3 mixture (0.4 M) of Acetic Acid, Hydrochloric Acid, 37% and Water was cooled to 0° C. and slowly treated with a 4 M solution of sodium nitrite in water. The reaction was stirred at 5° C. for 30 minutes then treated dropwise with a 2M solution of potassium iodide in water. The reaction evolved a gas and turned brown. The reaction was stirred 15 minutes at 0° C., 40 minutes at rt and 1 h at 60° C. The brown solid was filtered, dissolved in ethyl acetate and the solution washed with acidified sodium thiosulfate and then brine. The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. During evaporation, a precipitate appeared and was filtered. The mother liquors were evaporated further and 2 more crops were collected. The last mother liquor was transferred with diethyl ether and upon evaporation yields more products. The reaction was stirred 15 minutes at 0° C., 40 minutes at rt and 1 h at 60° C The brown solid was filtered dissolved in ethyl acetate the solution washed with acidified sodium thiosulfate The organic phase was dried over magnesium sulfate concentrated under reduced pressure During evaporation was filtered The mother liquors were evaporated further 2 more crops were collected The last mother liquor was transferred with diethyl ether and upon evaporation yields more products

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

Procedure: The title compound was prepared from tert-butyl 6-bromo-2-(1-(tert-butoxycarbonyl)-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (Preparation 10) and 2-chloro-4-(methylsulfonyl)aniline using the method described for Example 35. Purified using preparative TLC eluting with 20% ethyl acetate in CH2Cl2. 1H-NMR (500 MHz, DMSO-d6) 1.46, 1.60 (2×s, 9H each), 3.21 (s, 3H), 6.90 (s, 1H), 7.74 (dd, J=2.2, 8.9 Hz, 1H), 7.91 (d, J=2.30 Hz, 1H), 7.93 (s, 1H), 8.07 (s, 1H), 8.30 (d, J=8.5 Hz, 1H), 8.52 (s, 1H), 8.57 (s, 1H), 8.98 (s, 1H). Purified eluting with 20% ethyl acetate in CH2Cl2

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

Procedure: 2-Chloro-4-methylsulfonylaniline (2.06 g.) is diazotized and coupled with 3-(N-cyclohexyl-N-ethylamino)acetanilide (2.60 g.) in 40 ml. of 1:5 acid as described in Example 9, except that the coupling is buffered by the addition of ammonium acetate after the diazonium solution is added to the coupler. This azo compound, 2-(2-chloro-4-methylsulfonylphenylazo)-5-N-cyclohexyl-N-ethylamino)acetanilide, produces bright scarlet shades on polyester fibers. is added to the coupler

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-4-fluoroanisole (6.0 g), 2-chloro-4-methylsulphonylaniline (9.0 g), cesium carbonate (14.7 g), palladium acetate (0.33 g) and 2-(dicyclohexylphosphino)-2′,4′,6′-tri-1-propyl-1,1′-biphenyl (0.54 g) in dioxane (60 ml) was heated at 100° C. for 20 h. The mixture was cooled, and partitioned between ethylacetate/water. The organics were separated, washed with brine, dried and evaporated under reduced pressure. The residue was purified by chromatography on silica eluting with 25% ethylacetate/isohexane. Yield 3.2 g The mixture was cooled partitioned between ethylacetate/water The organics were separated washed with brine dried evaporated under reduced pressure The residue was purified by chromatography on silica eluting with 25% ethylacetate/isohexane

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-chloro-4-methylsulfonyl aniline (1.0 g, 4.9 mmol) in N-methylpyrrolidine (10 mL) was added copper (I) cyanide (4.35 g, 48.6 mmol) under nitrogen. The reaction mixture was stirred at 180° C. for 72 hours, cooled to room temperature, poured to a 1:1 mixture of ammonia and water (200 mL), stirred for 1 hour, and then filtered off. The residue was washed with CH2Cl2 (50 mL) and filtrate was extracted with CH2Cl2 (3×20 mL). The combined organic layers were backwashed with water (50 mL), dried over sodium sulfate, and concentrated to provide crude material, which was purified by flash column chromatography (silica gel; 230-400 mesh; ethyl acetate/hexanes=1:5) to obtain 2-amino-5-methanesulfonyl-benzonitrile as a white solid. Yield: 0.1 g (13%). A suspension of potassium hydroxide (2.05 g, 36.7 mmol) in ethylene glycol (9 mL) was heated to 80° C. KOH was dissolved completely at this stage. 2-Amino-5-methanesulfonyl-benzonitrile (0.900 g, 4.59 mmol) was added to the reaction mixture and the bath temperature was increased to 185° C. and stirred for 16 hours. The resultant reaction mixture was cooled to room temperature, diluted with water (20 mL), and extracted with CH2Cl2 (3×30 mL). The aqueous layer was acidified with 2 N HCl to pH 4-5, extracted with EtOAc (3×30 mL), and the combined organic layers were backwashed with water (30 mL), then brine (30 mL), dried over sodium sulfate, and evaporated, to obtain 2-amino-5-methanesulfonyl-benzoic acid. Yield: 0.750 g (75%). cooled to room temperature stirred for 1 hour filtered off The residue was washed with CH2Cl2 (50 mL) and filtrate was extracted with CH2Cl2 (3×20 mL) dried over sodium sulfate concentrated to provide crude material, which was purified by flash column chromatography (silica gel; 230-400 mesh; ethyl acetate/hexanes=1:5)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-4-fluoroanisole (6.0 g), 2-chloro-4-methylsulphonylaniline (9.0 g), cesium carbonate (14.7 g), palladium acetate (0.33 g) and 2-(dicyclohexylphosphino)-2′,4′,6′-tri-1-propyl-1,1′-biphenyl (0.54 g) in dioxane (60 ml) was heated at 100° C. for 20 h. The mixture was cooled, and partitioned between ethylacetate/water. The organics were separated, washed with brine, dried and evaporated under reduced pressure. The residue was purified by chromatography on silica eluting with 25% ethylacetate/isohexane. Yield 3.2 g The mixture was cooled partitioned between ethylacetate/water The organics were separated washed with brine dried evaporated under reduced pressure The residue was purified by chromatography on silica eluting with 25% ethylacetate/isohexane

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

Procedure: A solution of 2-chloro-4-(methanesulfonyl)aniline (25 g, 122 mmol) in acetonitrile (500 mL) was cooled to 0° C., then sodium nitrite (20.97 g, 303.9 mmol) and potassium iodide (50.45 g, 303.9 mmol) were added. After the reaction mixture was stirred for 30 minutes at 0° C., concentrated hydrochloric acid (50 mL) was added drop-wise via an addition funnel. The reaction was stirred at 0° C. for an additional 45 minutes. The reaction mixture was warmed to room temperature, then stirred for 2.5 hours. The reaction mixture was poured into ice water (800 mL), and extracted with dichloromethane. The organic layer was washed with water, dried over sodium sulfate, filtered, and concentrated. Flash chromatography (RediSep® Flash column, 230-400 mesh, 10%-35% ethyl acetate in hexane) gave 2-chloro-1-iodo-4-methanesulfonyl-benzene (13.88 g, 36%). 1H NMR (300 MHz, CDCl3) δ ppm 8.11 (d, J=8.4 Hz, 1 H), 8.00 (d, J=1.9 Hz, 1 H), 7.51 (dd, J=8.4, 1.9 Hz, 1 H), 3.07 (s, 3 H). The reaction was stirred at 0° C. for an additional 45 minutes The reaction mixture was warmed to room temperature stirred for 2.5 hours extracted with dichloromethane The organic layer was washed with water dried over sodium sulfate filtered concentrated

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

Procedure: 2-Chloro-4-methylsulfonylaniline (2.06 g.) is diazotized and coupled with 3-(N-cyclohexyl-N-ethylamino)acetanilide (2.60 g.) in 40 ml. of 1:5 acid as described in Example 9, except that the coupling is buffered by the addition of ammonium acetate after the diazonium solution is added to the coupler. This azo compound, 2-(2-chloro-4-methylsulfonylphenylazo)-5-N-cyclohexyl-N-ethylamino)acetanilide, produces bright scarlet shades on polyester fibers. is added to the coupler

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

Procedure: 2-Chloro-4-methylsulfonylaniline (2.06 g.) is diazotized and coupled with 3-(N-cyclohexyl-N-ethylamino)acetanilide (2.60 g.) in 40 ml. of 1:5 acid as described in Example 9, except that the coupling is buffered by the addition of ammonium acetate after the diazonium solution is added to the coupler. This azo compound, 2-(2-chloro-4-methylsulfonylphenylazo)-5-N-cyclohexyl-N-ethylamino)acetanilide, produces bright scarlet shades on polyester fibers. is added to the coupler