1-(4-chloro-2-methoxyphenyl)piperazine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: substituting 1-(4-chloro-2-methoxyphenyl)piperazine and 1-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione gave 1-{3-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]propyl}-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, m.p. 154°-155° C.; Anal.: Calcd. for C19H25ClN4O3.(HCl)2 : C, 44.05; H, 6.37; N, 10.81%; Found: C, 44.26; H, 6.08; N, 10.46%;

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: substituting 1-(4-chloro-2-methoxyphenyl)piperazine and 3-benzyl-1-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione gave 3-benzyl-1-{3-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]propyl}-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, m.p. 194°-195° C.; Anal.: Calcd. for C26H31ClN4O3.(HCl)2 : C, 55.63; H, 6.03; N, 9.98%; Found: C, 55.82; H, 5.94; N, 9.85%;

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione (223 mg, 0.98 mmol), prepared as in Example 19, and 1-(4-chloro-2-methoxyphenyl)piperazine (200 mg, 0.98 mmol), prepared as in Example 12, was heated 2 hours with stirring at 180° to 190° C., allowed to cool to 25° C. and then purified by preparative thin layer chromatography on silica gel eluting with methylene chloride/(methylene chloride/methanol/ammonium hydroxide-60:10:1) (7:3) to give 3-{3-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]propyl}-5-methyl-2,4(1H,3H)-pyrimidinedione. The free base was recrystallized from a solution of hydrogen chloride in methanol to give 3-{3-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]propyl}-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, m.p. 182°-184° C. Anal.: Calcd. for C19H25ClN4O3.(HCl)2 : C, 48.25; H, 5.92; N, 11.84%; Found: C, 48.55; H, 5.81; N, 11.85%. was heated 2 hours purified by preparative thin layer chromatography on silica gel eluting with methylene chloride/(methylene chloride/methanol/ammonium hydroxide-60:10:1) (7:3)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Title compound was prepared following the HATU mediated coupling protocol P, wherein 1-(4-Chloro-2-methoxyphenyl)-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) 7.02 (s, 1H), 6.93 (m, 2H), 5.36 (s, 2H), 3.82 (s, 3H), 3.60 (m, 4H), 3.03 (m, 2H), 2.95 (m, 2H), 2.19 (s, 3H) ppm; MS (ES) M+H expected=451.1, found=451.0.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Title compound was prepared following the HATU mediated coupling protocol P, wherein 1-(4-Chloro-2-methoxyphenyl)-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) 7.02 (s, 1H), 6.93 (m, 2H), 5.36 (s, 2H), 3.82 (s, 3H), 3.60 (m, 4H), 3.03 (m, 2H), 2.95 (m, 2H), 2.19 (s, 3H) ppm; MS (ES) M+H expected=451.1, found=451.0.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: substituting 1-(4-chloro-2-methoxyphenyl)piperazine and 1-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione gave 1-{3-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]propyl}-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, m.p. 154°-155° C.; Anal.: Calcd. for C19H25ClN4O3.(HCl)2 : C, 44.05; H, 6.37; N, 10.81%; Found: C, 44.26; H, 6.08; N, 10.46%;

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: substituting 1-(4-chloro-2-methoxyphenyl)piperazine and 3-benzyl-1-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione gave 3-benzyl-1-{3-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]propyl}-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, m.p. 194°-195° C.; Anal.: Calcd. for C26H31ClN4O3.(HCl)2 : C, 55.63; H, 6.03; N, 9.98%; Found: C, 55.82; H, 5.94; N, 9.85%;

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione (223 mg, 0.98 mmol), prepared as in Example 19, and 1-(4-chloro-2-methoxyphenyl)piperazine (200 mg, 0.98 mmol), prepared as in Example 12, was heated 2 hours with stirring at 180° to 190° C., allowed to cool to 25° C. and then purified by preparative thin layer chromatography on silica gel eluting with methylene chloride/(methylene chloride/methanol/ammonium hydroxide-60:10:1) (7:3) to give 3-{3-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]propyl}-5-methyl-2,4(1H,3H)-pyrimidinedione. The free base was recrystallized from a solution of hydrogen chloride in methanol to give 3-{3-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]propyl}-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, m.p. 182°-184° C. Anal.: Calcd. for C19H25ClN4O3.(HCl)2 : C, 48.25; H, 5.92; N, 11.84%; Found: C, 48.55; H, 5.81; N, 11.85%. was heated 2 hours purified by preparative thin layer chromatography on silica gel eluting with methylene chloride/(methylene chloride/methanol/ammonium hydroxide-60:10:1) (7:3)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione (223 mg, 0.98 mmol), prepared as in Example 19, and 1-(4-chloro-2-methoxyphenyl)piperazine (200 mg, 0.98 mmol), prepared as in Example 12, was heated 2 hours with stirring at 180° to 190° C., allowed to cool to 25° C. and then purified by preparative thin layer chromatography on silica gel eluting with methylene chloride/(methylene chloride/methanol/ammonium hydroxide-60:10:1) (7:3) to give 3-{3-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]propyl}-5-methyl-2,4(1H,3H)-pyrimidinedione. The free base was recrystallized from a solution of hydrogen chloride in methanol to give 3-{3-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]propyl}-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, m.p. 182°-184° C. Anal.: Calcd. for C19H25ClN4O3.(HCl)2 : C, 48.25; H, 5.92; N, 11.84%; Found: C, 48.55; H, 5.81; N, 11.85%. was heated 2 hours purified by preparative thin layer chromatography on silica gel eluting with methylene chloride/(methylene chloride/methanol/ammonium hydroxide-60:10:1) (7:3)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Title compound was prepared following the HATU mediated coupling protocol P, wherein 1-(4-Chloro-2-methoxyphenyl)-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) 7.02 (s, 1H), 6.93 (m, 2H), 5.36 (s, 2H), 3.82 (s, 3H), 3.60 (m, 4H), 3.03 (m, 2H), 2.95 (m, 2H), 2.19 (s, 3H) ppm; MS (ES) M+H expected=451.1, found=451.0.

反応条件: temp:0.00; pressure:0.00; stir: