(4-amino-2-chloro-3-methylphenyl) thiocyanate

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

Procedure: Crude 4-amino-2-chloro-3-methylphenyl thiocyanate (600 mg, 3.0 mmol) was dissolved in a mixture of methanol:water (2:1, 22 mL) and cooled to 0° C. Sodium hydrosulfide monohydrate (338 mg, 4.6 mmol) and sodium borohydride (447 mg, 11.8 mmol) were added then the mixture was allowed to warm to room temperature and stir overnight. After this time sodium hydroxide (96 mg, 2 4 mmol) was added followed by 2,4-dichloropyrimidine (360 mg, 2 4 mmol) and the mixture allowed to stir for a further 24h. The methanol was removed in vacuo and then the mixture was extracted with ethyl acetate. The extracts were dried (Na2SO4) and evaporated then the residue was purified by flash chromatography to afford 3-chloro-4-[(2-chloropyrimidin-4-yl)thio]-2-methylaniline (353 mg, 41%). to warm to room temperature to stir for a further 24h The methanol was removed in vacuo the mixture was extracted with ethyl acetate The extracts were dried (Na2SO4) evaporated the residue was purified by flash chromatography

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

Procedure: To a stirred solution of ammonium thiocyanate (1.61 g, 0.02 mol) and iodine (1.79 g, 7.1 mmol) in methanol was added 3-chloro-2-methylaniline (0.84 mL, 7.1 mmol) dropwise. The mixture was allowed to stir at room temperature for 2 days after which time water (50 mL) was added and the mixture was extracted with dichloromethane (4×50 mL). The extracts were washed with a 15% aqueous solution of sodium thiosulfate (100 mL) then dried (Na2SO4) and the solvent removed in vacuo to afford 4-amino-2-chloro-3-methylphenyl thiocyanate as a brown solid (1.26 g, 90%). Material was used crude in subsequent steps. was added the mixture was extracted with dichloromethane (4×50 mL) The extracts were washed with a 15% aqueous solution of sodium thiosulfate (100 mL) then dried (Na2SO4) the solvent removed in vacuo

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

Procedure: To a stirred solution of ammonium thiocyanate (1.61 g, 0.02 mol) and iodine (1.79 g, 7.1 mmol) in methanol was added 3-chloro-2-methylaniline (0.84 mL, 7.1 mmol) dropwise. The mixture was allowed to stir at room temperature for 2 days after which time water (50 mL) was added and the mixture was extracted with dichloromethane (4×50 mL). The extracts were washed with a 15% aqueous solution of sodium thiosulfate (100 mL) then dried (Na2SO4) and the solvent removed in vacuo to afford 4-amino-2-chloro-3-methylphenyl thiocyanate as a brown solid (1.26 g, 90%). Material was used crude in subsequent steps. was added the mixture was extracted with dichloromethane (4×50 mL) The extracts were washed with a 15% aqueous solution of sodium thiosulfate (100 mL) then dried (Na2SO4) the solvent removed in vacuo

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

Procedure: Crude 4-amino-2-chloro-3-methylphenyl thiocyanate (600 mg, 3.0 mmol) was dissolved in a mixture of methanol:water (2:1, 22 mL) and cooled to 0° C. Sodium hydrosulfide monohydrate (338 mg, 4.6 mmol) and sodium borohydride (447 mg, 11.8 mmol) were added then the mixture was allowed to warm to room temperature and stir overnight. After this time sodium hydroxide (96 mg, 2.4 mmol) was added followed by 2,4-dichloropyrimidine (360 mg, 2.4 mmol) and the mixture allowed to stir for a further 24 h. The methanol was removed in vacuo and then the mixture was extracted with ethyl acetate. The extracts were dried (Na2SO4) and evaporated then the residue was purified by flash chromatography to afford 3-chloro-4-[(2-chloropyrimidin-4-yl)thio]-2-methylaniline (353 mg, 41%). to warm to room temperature to stir for a further 24 h The methanol was removed in vacuo the mixture was extracted with ethyl acetate The extracts were dried (Na2SO4) evaporated the residue was purified by flash chromatography

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

Procedure: To a stirred solution of ammonium thiocyanate (1.61 g, 0.02 mol) and iodine (1.79 g, 7.1 mmol) in methanol was added 3-chloro-2-methylaniline (0.84 mL, 7.1 mmol) dropwise. The mixture was allowed to stir at room temperature for 2 days after which time water (50 mL) was added and the mixture was extracted with dichloromethane (4×50 mL). The extracts were washed with a 15% aqueous solution of sodium thiosulfate (100 mL) then dried (Na2SO4) and the solvent removed in vacuo to afford 4-amino-2-chloro-3-methylphenyl thiocyanate as a brown solid (1.26 g, 90%). Material was used crude in subsequent steps. was added the mixture was extracted with dichloromethane (4×50 mL) The extracts were washed with a 15% aqueous solution of sodium thiosulfate (100 mL) then dried (Na2SO4) the solvent removed in vacuo

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

Procedure: Crude 4-amino-2-chloro-3-methylphenyl thiocyanate (600 mg, 3.0 mmol) was dissolved in a mixture of methanol:water (2:1, 22 mL) and cooled to 0° C. Sodium hydrosulfide monohydrate (338 mg, 4.6 mmol) and sodium borohydride (447 mg, 11.8 mmol) were added then the mixture was allowed to warm to room temperature and stir overnight. After this time sodium hydroxide (96 mg, 2 4 mmol) was added followed by 2,4-dichloropyrimidine (360 mg, 2 4 mmol) and the mixture allowed to stir for a further 24h. The methanol was removed in vacuo and then the mixture was extracted with ethyl acetate. The extracts were dried (Na2SO4) and evaporated then the residue was purified by flash chromatography to afford 3-chloro-4-[(2-chloropyrimidin-4-yl)thio]-2-methylaniline (353 mg, 41%). to warm to room temperature to stir for a further 24h The methanol was removed in vacuo the mixture was extracted with ethyl acetate The extracts were dried (Na2SO4) evaporated the residue was purified by flash chromatography

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

Procedure: To a stirred solution of ammonium thiocyanate (1.61 g, 0.02 mol) and iodine (1.79 g, 7.1 mmol) in methanol was added 3-chloro-2-methylaniline (0.84 mL, 7.1 mmol) dropwise. The mixture was allowed to stir at room temperature for 2 days after which time water (50 mL) was added and the mixture was extracted with dichloromethane (4×50 mL). The extracts were washed with a 15% aqueous solution of sodium thiosulfate (100 mL) then dried (Na2SO4) and the solvent removed in vacuo to afford 4-amino-2-chloro-3-methylphenyl thiocyanate as a brown solid (1.26 g, 90%). Material was used crude in subsequent steps. was added the mixture was extracted with dichloromethane (4×50 mL) The extracts were washed with a 15% aqueous solution of sodium thiosulfate (100 mL) then dried (Na2SO4) the solvent removed in vacuo