N-tert-butyl-3-(chloromethyl)benzamide

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

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

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

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

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

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

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

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

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

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

Procedure: To (4-amino-3-fluorophenyl)(3,3-dimethylpiperazin-1-yl)methanone (0.521 mmol, 131 mg) in acetonitrile (5.213 mL) was added N-tert-butyl-3-(chloromethyl)benzamide (0.573 mmol, 129 mg), and triethylamine (1.040 mmol, 145 μl, 105 mg). A catalytic amount of sodium iodide was added. The mixture was heated to reflux for 3 hours. The mixture was allowed to cool and ethyl acetate was added. The organic mixture was washed with water, dried with sodium sulfate, filtered and concentrated under vacuum. The residue was purified by silica chromatography (eluting with 5% methanol in dichloromethane) to yield the title compound (90 mg). MS (ESI) m/z 441.4 [M+H]+ The mixture was heated to reflux for 3 hours to cool The organic mixture was washed with water dried with sodium sulfate filtered concentrated under vacuum The residue was purified by silica chromatography (eluting with 5% methanol in dichloromethane)

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

Procedure: A stirred mixture of (3-fluoro-4-nitrophenyl)(3-(fluoromethyl)piperazin-1-yl)methanone (456 mg, 1.6 mmol), N-tert-butyl-3-(chloromethyl)benzamide (361 mg, 1.6 mmol), triethylamine (3.1 mmol, 341 mg) and sodium iodide (1.6 mmol, 240 mg) in acetonitrile (10 mL) was heated to 60° C. for several hours. The reaction was concentrated under reduced pressure. The residue was then dissolved in dichloromethane and extracted with water (×3). The organic phase was dried (sodium sulfate) and concentrated under vacuum. The crude material was purified using silica chromatography to give the title compound (435 mg). MS (ESI) m/z 475.7[M+H]+ The reaction was concentrated under reduced pressure The residue was then dissolved in dichloromethane extracted with water (×3) The organic phase was dried (sodium sulfate) concentrated under vacuum The crude material was purified

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

Procedure: (S)-(4-Amino-3-fluorophenyl)(3-isopropylpiperazin-1-yl)methanone (0.754 mmol, 200 mg), N-tert-butyl-3-(chloromethyl)benzamide (0,754 mmol, 170 mg), potassium carbonate (1.508 mmol, 208 mg) and sodium iodide (0.075 mmol, 11.30 mg) were dissolved in acetonitrile (20 mL) and heated at reflux for 3 hours. The reaction was concentrated under vacuum and the crude material dissolved in ethyl acetate and washed with water, dried over sodium sulphate and concentration under vacuum. The crude residue was then purified by column chromatography (eluting with dichloromethane to dichloromethane/methanol (1% to 5%)) to give the title compound (160 mg) as an off white solid. MS (ESI) m/z 456.4 [M+H]+ heated at reflux for 3 hours The reaction was concentrated under vacuum the crude material dissolved in ethyl acetate washed with water dried over sodium sulphate and concentration under vacuum The crude residue was then purified by column chromatography (eluting with dichloromethane to dichloromethane/methanol (1% to 5%))