1-(5-fluoro-2-methoxyphenyl)piperazine

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

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

Procedure: Title compound was prepared following the HATU mediated coupling protocol P, wherein 1-(2-Methoxy-5-fluorophenyl)piperazine and (4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid were used as the coupling components, to give the product as a solid: 1H NMR (DMSO-d6, 400 MHz) 6.93 (m, 1H), 6.77 (m, 3H), 5.36 (s, 2H), 3.77 (s, 3H), 3.59 (m, 4H), 3.07 (m, 2H), 2.98 (m, 2H), 2.19 (s, 3H) ppm; MS (ES) M+H expect 435.1, found 435.0.

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

Procedure: Title compound was prepared following the HATU mediated coupling protocol P, wherein 1-(2-Methoxy-5-fluorophenyl)piperazine and (4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid were used as the coupling components, to give the product as a solid: 1H NMR (DMSO-d6, 400 MHz) 6.93 (m, 1H), 6.77 (m, 3H), 5.36 (s, 2H), 3.77 (s, 3H), 3.59 (m, 4H), 3.07 (m, 2H), 2.98 (m, 2H), 2.19 (s, 3H) ppm; MS (ES) M+H expect 435.1, found 435.0.

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

Procedure: A mixture of the 4-(5-fluoro-2-methoxyphenyl)-piperazine (2.1 g, 10.0 mmole, prepared by method disclosed in U.S. Pat. No. 4,585,773), 1-(8-aza-bicyclo[3.2.1]oct-8-yl)-4-chloro-2-phenyl-butan-1-one (3.40 g, 10.0 mmole), diisopropylethylamine (1.4 g, 11.0 mmole) and potassium iodide (1.66 g, 10.0 mmole) was heated in dimethylformamide (35 mL) to 80° C. for 5 hours. After cooling to ambient temperature, the mixture was poured into water (100 mL) and extracted with ethyl acetate (2×300 mL). The combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to give crude product. Purification of this material by column chromatoghaphy (silica gel with 2% methanol in ethyl acetate as eluant) followed by the treatment with 1.1 equivalent of 1N hydrogen chloride in ether gave 1.3 g of the title compound as the hydrochloride quarter hydrate, m.p. 203°-206° C. prepared by method extracted with ethyl acetate (2×300 mL) The combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL) dried over anhydrous magnesium sulfate filtered concentrated under vacuum to give crude product Purification of this material by column chromatoghaphy (silica gel with 2% methanol in ethyl acetate as eluant)

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

Procedure: A mixture of the 4-(5-fluoro-2-methoxyphenyl)-piperazine (2.1 g, 10.0 mmole, prepared by method disclosed in U.S. Pat. No. 4,585,773), 1-(8-aza-bicyclo[3.2.1]oct-8-yl)-4-chloro-2-phenyl-butan-1-one (3.40 g, 10.0 mmole), diisopropylethylamine (1.4 g, 11.0 mmole) and potassium iodide (1.66 g, 10.0 mmole) was heated in dimethylformamide (35 mL) to 80° C. for 5 hours. After cooling to ambient temperature, the mixture was poured into water (100 mL) and extracted with ethyl acetate (2×300 mL). The combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to give crude product. Purification of this material by column chromatoghaphy (silica gel with 2% methanol in ethyl acetate as eluant) followed by the treatment with 1.1 equivalent of 1N hydrogen chloride in ether gave 1.3 g of the title compound as the hydrochloride quarter hydrate, m.p. 203°-206° C. prepared by method extracted with ethyl acetate (2×300 mL) The combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL) dried over anhydrous magnesium sulfate filtered concentrated under vacuum to give crude product Purification of this material by column chromatoghaphy (silica gel with 2% methanol in ethyl acetate as eluant)

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

Procedure: Title compound was prepared following the HATU mediated coupling protocol P, wherein 1-(2-Methoxy-5-fluorophenyl)piperazine and (4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid were used as the coupling components, to give the product as a solid: 1H NMR (DMSO-d6, 400 MHz) 6.93 (m, 1H), 6.77 (m, 3H), 5.36 (s, 2H), 3.77 (s, 3H), 3.59 (m, 4H), 3.07 (m, 2H), 2.98 (m, 2H), 2.19 (s, 3H) ppm; MS (ES) M+H expect 435.1, found 435.0.

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

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

Procedure: Title compound was prepared following the HATU mediated coupling protocol P, wherein 1-(2-Methoxy-5-fluorophenyl)piperazine and (4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid were used as the coupling components, to give the product as a solid: 1H NMR (DMSO-d6, 400 MHz) 6.93 (m, 1H), 6.77 (m, 3H), 5.36 (s, 2H), 3.77 (s, 3H), 3.59 (m, 4H), 3.07 (m, 2H), 2.98 (m, 2H), 2.19 (s, 3H) ppm; MS (ES) M+H expect 435.1, found 435.0.

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

Procedure: A mixture of the 4-(5-fluoro-2-methoxyphenyl)-piperazine (2.1 g, 10.0 mmole, prepared by method disclosed in U.S. Pat. No. 4,585,773), 1-(8-aza-bicyclo[3.2.1]oct-8-yl)-4-chloro-2-phenyl-butan-1-one (3.40 g, 10.0 mmole), diisopropylethylamine (1.4 g, 11.0 mmole) and potassium iodide (1.66 g, 10.0 mmole) was heated in dimethylformamide (35 mL) to 80° C. for 5 hours. After cooling to ambient temperature, the mixture was poured into water (100 mL) and extracted with ethyl acetate (2×300 mL). The combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to give crude product. Purification of this material by column chromatoghaphy (silica gel with 2% methanol in ethyl acetate as eluant) followed by the treatment with 1.1 equivalent of 1N hydrogen chloride in ether gave 1.3 g of the title compound as the hydrochloride quarter hydrate, m.p. 203°-206° C. prepared by method extracted with ethyl acetate (2×300 mL) The combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL) dried over anhydrous magnesium sulfate filtered concentrated under vacuum to give crude product Purification of this material by column chromatoghaphy (silica gel with 2% methanol in ethyl acetate as eluant)

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

Procedure: Title compound was prepared following the HATU mediated coupling protocol P, wherein 1-(2-Methoxy-5-fluorophenyl)piperazine and (4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid were used as the coupling components, to give the product as a solid: 1H NMR (DMSO-d6, 400 MHz) 6.93 (m, 1H), 6.77 (m, 3H), 5.36 (s, 2H), 3.77 (s, 3H), 3.59 (m, 4H), 3.07 (m, 2H), 2.98 (m, 2H), 2.19 (s, 3H) ppm; MS (ES) M+H expect 435.1, found 435.0.