4-bromo-2-chloro-5-(trifluoromethoxy)aniline

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-3-trifluoromethoxy-phenylamine (2.0 g, 7.8 mmol) in ACN (60 mL) was slowly added a solution of N-chlorosuccinimide (1.0 g, 7.8 mmol) in ACN (40 mL). The reaction mixture was heated at 60° C. overnight and extracted with ethyl actetate/water. The organic layer was dried over sodium sulfate and purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc: hexanes) to produce the desired product as an orange-ish-colored oil (1.4 g, 64% yield). extracted with ethyl actetate/water The organic layer was dried over sodium sulfate purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc: hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-3-trifluoromethoxy-phenylamine (2.0 g, 7.8 mmol) in ACN (60 mL) was slowly added a solution of N-chlorosuccinimide (1.0 g, 7.8 mmol) in ACN (40 mL). The reaction mixture was heated at 60° C. overnight and extracted with ethyl actetate/water. The organic layer was dried over sodium sulfate and purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc: hexanes) to produce the desired product as an orange-ish-colored oil (1.4 g, 64% yield). extracted with ethyl actetate/water The organic layer was dried over sodium sulfate purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc: hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-3-trifluoromethoxy-phenylamine (2.0 g, 7.8 mmol) in ACN (60 mL) was slowly added a solution of N-chlorosuccinimide (1.0 g, 7.8 mmol) in ACN (40 mL). The reaction mixture was heated at 60° C. overnight and extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate and purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc:hexanes) to produce the desired product as an orange-ish-colored oil (1.4 g, 64% yield). extracted with ethyl acetate/water The organic layer was dried over sodium sulfate purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc:hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-3-trifluoromethoxy-phenylamine (2.0 g, 7.8 mmol) in ACN (60 mL) was slowly added a solution of N-chlorosuccinimide (1.0 g, 7.8 mmol) in ACN (40 mL). The reaction mixture was heated at 60° C. overnight and extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate and purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc: hexanes) to produce the desired product as an orange-ish_colored oil (1.4 g, 64% yield). extracted with ethyl acetate/water The organic layer was dried over sodium sulfate purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc: hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-3-trifluoromethoxy-phenylamine (2.0 g, 7.8 mmol) in ACN (60 mL) was slowly added a solution of N-chlorosuccinimide (1.0 g, 7.8 mmol) in ACN (40 mL). The reaction mixture was heated at 60° C. overnight and extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate and purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc:hexanes) to produce the desired product as an orange-ish colored oil (1.4 g, 64% yield). extracted with ethyl acetate/water The organic layer was dried over sodium sulfate purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc:hexanes)

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

Procedure: To a solution of 4-bromo-2-chloro-5-trifluoromethoxy-phenylamine (92.5 mg, 0.32 mmol) in DCM (0.82 mL) was added CDI (56.8 mg, 0.35 mmol). The reaction mixture was stirred at RT for 6 h and a solution of (S)-3-methyl-4-piperidin-4-yl-piperazine-1-carboxylic acid tert-butyl ester (99.3 mg, 0.35 mmol; Preparation 22) in DCM (1 mL) was added. The solution was concentrated under vacuum and purified by silica gel chromatography (0-5% MeOH/DCM). Product fractions were combined and concentrated under vacuum to provide the title intermediate (32 mg, 17% yield) as a clear oil. (m/z): [M+H]+ calcd for C23H31BrClF3N4O4 599.12, 601.11 found 601.4. The solution was concentrated under vacuum purified by silica gel chromatography (0-5% MeOH/DCM) concentrated under vacuum

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

Procedure: To a solution of 4-bromo-2-chloro-5-trifluoromethoxy-phenylamine (0.55 g, 1.90 mmol) in DCM (4.9 mL) was added CDI (0.34 g, 2.09 mmol). The reaction solution was stirred at RT overnight and then 4-piperazin-1-yl-piperidine-1-carboxylic acid tert-butyl ester (0.56 g, 2.09 mmol; Preparation 12) was added and the reaction mixture was stirred for 30 min at RT, concentrated under vacuum and purified by silica gel chromatography (0-5% MeOH/DCM). Pure fractions were combined and concentrated under vacuum to provide the title intermediate (0.67 g, 60% yield) as a white foam. (m/z): [M+H]+ calcd for C22H29BrClF3N4O4 585.1 found 584.6. the reaction mixture was stirred for 30 min at RT concentrated under vacuum purified by silica gel chromatography (0-5% MeOH/DCM) concentrated under vacuum

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-3-trifluoromethoxy-phenylamine (2.0 g, 7.8 mmol) in ACN (60 mL) was slowly added a solution of N-chlorosuccinimide (1.0 g, 7.8 mmol) in ACN (40 mL). The reaction mixture was heated to at 60° C. overnight and extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate and purified by silica gel chromatography (40 g silica, 100% hexanes to 10% EtOAc: hexanes) to produce the desired product as an orange colored oil (1.4 g, 64% yield). extracted with ethyl acetate/water The organic layer was dried over sodium sulfate purified by silica gel chromatography (40 g silica, 100% hexanes to 10% EtOAc: hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-3-trifluoromethoxy-phenylamine (2.0 g, 7.8 mmol) in ACN (60 mL) was slowly added a solution of N-chlorosuccinimide (1.0 g, 7.8 mmol) in ACN (40 mL). The reaction mixture was heated at 60° C. overnight and extracted with ethyl actetate/water. The organic layer was dried over sodium sulfate and purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc:hexanes) to produce the desired product as an orange-ish colored oil (1.4 g, 64% yield). extracted with ethyl actetate/water The organic layer was dried over sodium sulfate purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc:hexanes)