N-(3-amino-5-bromophenyl)acetamide

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

Procedure: To a solution of N-(3-amino-5-bromophenyl)acetamide (3.25 g, 14.19 mmol) and 2-chloro-4-(trifluoromethyl)pyrimidine (2.054 mL, 17.03 mmol) in dioxane (8.5 mL) under nitrogen, was added pTsOH (2.70 g, 14.19 mmol). The reaction was stirred at 100° C. for 18 h, cooled to at room temperature. Solvent was removed under reduced pressure and the resultant residue was diluted with sat. NaH-CO3 (aq) and DCM. The organic was dried over sodium sulfate and was concentrated to dryness. Purified by flash chromatography (1:1 to 0:100 hexanes:ethyl acetate) to yield N-(3-bromo-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)acetamide (2.71 g, 7.22 mmol, 51%) as a beige powder. MS APCI: [M+H]m/z 377.0. cooled to at room temperature Solvent was removed under reduced pressure the resultant residue was diluted with sat. NaH-CO3 (aq) and DCM The organic was dried over sodium sulfate was concentrated to dryness Purified by flash chromatography (1:1 to 0:100 hexanes:ethyl acetate)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(3-bromo-5-nitrophenyl)acetamide (4 g, 15.44 mmol) was dissolved in ethanol (154 mL) and saturated NH4Cl(aq) (2 mL). Iron (2.59 g, 46.3 mmol) was added to the solution the reaction mixture was heated to 80° C. for 30 minutes. Upon completion, the reaction was cooled to room temperature and filtered through a short pad of silica gel (ethyl acetate wash). The organic was dried over sodium sulfate, filtered, and concentrated under reduced pressure. N-(3-amino-5-bromophenyl)acetamide was isolated as a beige foam (3.25 g, 14.19 mmol, 92%). Upon completion, the reaction was cooled to room temperature filtered through a short pad of silica gel (ethyl acetate wash) The organic was dried over sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(3-bromo-5-nitrophenyl)acetamide (4 g, 15.44 mmol) was dissolved in ethanol (154 mL) and saturated NH4Cl(aq) (2 mL). Iron (2.59 g, 46.3 mmol) was added to the solution the reaction mixture was heated to 80° C. for 30 minutes. Upon completion, the reaction was cooled to room temperature and filtered through a short pad of silica gel (ethyl acetate wash). The organic was dried over sodium sulfate, filtered, and concentrated under reduced pressure. N-(3-amino-5-bromophenyl)acetamide was isolated as a beige foam (3.25 g, 14.19 mmol, 92%). Upon completion, the reaction was cooled to room temperature filtered through a short pad of silica gel (ethyl acetate wash) The organic was dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: A solution of 4-(4-fluoro-3-nitrophenyl)-1-methyl-1H-pyrazole (1.6 g, 7.239 mmol), N-(3-amino-5-bromophenyl)acetamide (1.98 g, 8.687 mmol) and potassium fluoride (0.503 g, 8.687 mmol) in DMF was heated at 130° C. for 48 h. The mixture was quenched and extracted as in Example 1(d). The solvent was distilled off to afford the crude residue which was purified by column chromatography (60-120 silica gel, 50% ethyl acetate in hexane) to yield the title product in 35% yield (1.1 g); LC-MS (API): Calculated mass: 430.1; Observed mass: 432 [M+H]+ (rt: 1.50 min). The mixture was quenched extracted as in Example 1(d) The solvent was distilled off to afford the crude residue which was purified by column chromatography (60-120 silica gel, 50% ethyl acetate in hexane)

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

Procedure: A solution of 4-(4-fluoro-3-nitrophenyl)-1-methyl-1H-pyrazole (1.6 g, 7.239 mmol), N-(3-amino-5-bromophenyl)acetamide (1.98 g, 8.687 mmol) and potassium fluoride (0.503 g, 8.687 mmol) in DMF was heated at 130° C. for 48 h. The mixture was quenched and extracted as in Example 1(d). The solvent was distilled off to afford the crude residue which was purified by column chromatography (60-120 silica gel, 50% ethyl acetate in hexane) to yield the title product in 35% yield (1.1 g); LC-MS (API): Calculated mass: 430.1; Observed mass: 432 [M+H]+ (rt: 1.50 min). The mixture was quenched extracted as in Example 1(d) The solvent was distilled off to afford the crude residue which was purified by column chromatography (60-120 silica gel, 50% ethyl acetate in hexane)

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

Procedure: To a solution of N-(3-amino-5-bromophenyl)acetamide (3.25 g, 14.19 mmol) and 2-chloro-4-(trifluoromethyl)pyrimidine (2.054 mL, 17.03 mmol) in dioxane (8.5 mL) under nitrogen, was added pTsOH (2.70 g, 14.19 mmol). The reaction was stirred at 100° C. for 18 h, cooled to at room temperature. Solvent was removed under reduced pressure and the resultant residue was diluted with sat. NaH-CO3 (aq) and DCM. The organic was dried over sodium sulfate and was concentrated to dryness. Purified by flash chromatography (1:1 to 0:100 hexanes:ethyl acetate) to yield N-(3-bromo-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)acetamide (2.71 g, 7.22 mmol, 51%) as a beige powder. MS APCI: [M+H]m/z 377.0. cooled to at room temperature Solvent was removed under reduced pressure the resultant residue was diluted with sat. NaH-CO3 (aq) and DCM The organic was dried over sodium sulfate was concentrated to dryness Purified by flash chromatography (1:1 to 0:100 hexanes:ethyl acetate)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(3-bromo-5-nitrophenyl)acetamide (4 g, 15.44 mmol) was dissolved in ethanol (154 mL) and saturated NH4Cl(aq) (2 mL). Iron (2.59 g, 46.3 mmol) was added to the solution the reaction mixture was heated to 80° C. for 30 minutes. Upon completion, the reaction was cooled to room temperature and filtered through a short pad of silica gel (ethyl acetate wash). The organic was dried over sodium sulfate, filtered, and concentrated under reduced pressure. N-(3-amino-5-bromophenyl)acetamide was isolated as a beige foam (3.25 g, 14.19 mmol, 92%). Upon completion, the reaction was cooled to room temperature filtered through a short pad of silica gel (ethyl acetate wash) The organic was dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: A solution of 4-(4-fluoro-3-nitrophenyl)-1-methyl-1H-pyrazole (1.6 g, 7.239 mmol), N-(3-amino-5-bromophenyl)acetamide (1.98 g, 8.687 mmol) and potassium fluoride (0.503 g, 8.687 mmol) in DMF was heated at 130° C. for 48 h. The mixture was quenched and extracted as in Example 1(d). The solvent was distilled off to afford the crude residue which was purified by column chromatography (60-120 silica gel, 50% ethyl acetate in hexane) to yield the title product in 35% yield (1.1 g); LC-MS (API): Calculated mass: 430.1; Observed mass: 432 [M+H]+ (rt: 1.50 min). The mixture was quenched extracted as in Example 1(d) The solvent was distilled off to afford the crude residue which was purified by column chromatography (60-120 silica gel, 50% ethyl acetate in hexane)