(4-chlorophenyl)methanesulfonyl chloride

反応条件: temp:0.00; pressure:0.00; stir:

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: Production Example 3 was repeated except that 1-(4-methoxyphenyl)piperazine dihydrochloride and isovaleryl chloride were replaced with 1-(2,5-difluoro-4-methoxyphenyl)-piperazine (228 mg) and 4-chlorobenzylsulfonyl chloride (338 mg), respectively, to provide crude 1-(4-chlorobenzylsulfonyl)-4-(2,5-difluoro-4-methoxyphenyl)piperazine (419 mg).

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

実験手順: Production Example 3 was repeated except that 1-(4-methoxyphenyl)piperazine dihydrochloride and isovaleryl chloride were replaced with 1-(2,5-difluoro-4-methoxyphenyl)-piperazine (228 mg) and 4-chlorobenzylsulfonyl chloride (338 mg), respectively, to provide crude 1-(4-chlorobenzylsulfonyl)-4-(2,5-difluoro-4-methoxyphenyl)piperazine (419 mg).

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

実験手順: By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione obtained in Example 1, (3), and 4-chlorobenzylsulfonyl chloride, the title compound (yield 56%) was obtained in the same manner as that of Example 145.

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

実験手順: The title compound was prepared following the procedure described for Example 6 starting from 100 mg (0.256 mmol) tert-butyl 3-amino-5-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazole-1-carboxylate (Example 3A) and 346 mg (1.54 mmol) (4-chlorophenyl)methane-sulfonyl chloride. Yield: 4 mg (3% of th.).

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

実験手順: The title compound was prepared following the procedure described for Example 6 starting from 100 mg (0.256 mmol) tert-butyl 3-amino-5-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazole-1-carboxylate (Example 3A) and 346 mg (1.54 mmol) (4-chlorophenyl)methane-sulfonyl chloride. Yield: 4 mg (3% of th.).

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

実験手順: A solution of (2-amino-ethyl)-{2-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-dimethyl-ammonium bromide (Intermediate K) (0.3 g, 0.78 mmol), (4-chloro-phenyl)-methanesulfonyl chloride (0.18 g, 0.78 mmol) and N-methylmorpholine (0.35 mL, 3.18 mmol) in DMF (5 mL) is shaken at RT for 16 h. After this time the solvent is removed in vacuo and the residue is subjected to chromatography (basic alumina, 0-15% methanol in DCM) to yield the title compound. M+ 490. After this time the solvent is removed in vacuo

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

実験手順: A solution of (2-amino-ethyl)-{2-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-dimethyl-ammonium bromide (Intermediate K) (0.3 g, 0.78 mmol), (4-chloro-phenyl)-methanesulfonyl chloride (0.18 g, 0.78 mmol) and N-methylmorpholine (0.35 mL, 3.18 mmol) in DMF (5 mL) is shaken at RT for 16 h. After this time the solvent is removed in vacuo and the residue is subjected to chromatography (basic alumina, 0-15% methanol in DCM) to yield the title compound. M+ 490. After this time the solvent is removed in vacuo

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

実験手順: 3-Azido-5-isopropyl-azepan-2-one (70 mg, 0.36 mmol) was dissolved in ethanol/water (2:1 v/v) and hydrogenated over 10% Pd-c (5 mg) for 2 h. The reaction mixture was filtered and concentrated under reduced pressure. The residue was taken up in dry CH2Cl2 (5 ml) and Hünig's base (0.09 ml, 0.54 mmol) was added and this mixture was cooled (ice-bath) followed by the dropwise addition of 4-chlorobenzylsulfonyl chloride (90.3 mg, 0.43 mmol) in CH2Cl2 (0.5 ml). The reaction mixture was stirred at r.t. for 1 h and then diluted with CH2Cl2 and washed with NaHCO3 (1/2 sat., 3×), 5% KHSO4/10% K2SO4 (3×), water, brine, dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure and the crude product was purified over silica gel (ethyl acetate/n-heptane 1:2 to 1:1): white solid 0.08 g (75%); MS: m/e=343.0 (MH−) The reaction mixture was filtered concentrated under reduced pressure this mixture was cooled (ice-bath) washed with NaHCO3 (1/2 sat., 3×), 5% KHSO4/10% K2SO4 (3×), water, brine dried (MgSO4) filtered The filtrate was concentrated under reduced pressure the crude product was purified over silica gel (ethyl acetate/n-heptane 1:2 to 1:1)

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

実験手順: 3-Azido-5-isopropyl-azepan-2-one (70 mg, 0.36 mmol) was dissolved in ethanol/water (2:1 v/v) and hydrogenated over 10% Pd-c (5 mg) for 2 h. The reaction mixture was filtered and concentrated under reduced pressure. The residue was taken up in dry CH2Cl2 (5 ml) and Hünig's base (0.09 ml, 0.54 mmol) was added and this mixture was cooled (ice-bath) followed by the dropwise addition of 4-chlorobenzylsulfonyl chloride (90.3 mg, 0.43 mmol) in CH2Cl2 (0.5 ml). The reaction mixture was stirred at r.t. for 1 h and then diluted with CH2Cl2 and washed with NaHCO3 (1/2 sat., 3×), 5% KHSO4/10% K2SO4 (3×), water, brine, dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure and the crude product was purified over silica gel (ethyl acetate/n-heptane 1:2 to 1:1): white solid 0.08 g (75%); MS: m/e=343.0 (MH−) The reaction mixture was filtered concentrated under reduced pressure this mixture was cooled (ice-bath) washed with NaHCO3 (1/2 sat., 3×), 5% KHSO4/10% K2SO4 (3×), water, brine dried (MgSO4) filtered The filtrate was concentrated under reduced pressure the crude product was purified over silica gel (ethyl acetate/n-heptane 1:2 to 1:1)

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

実験手順: The title compound was prepared from (4-chlorophenyl)methanesulfonyl chloride and 1,1-dimethylpropargylamine according to the procedure described for Intermediate 4 replacing ethylamine by methylamine in the last step. 1H-NMR (DMSO-d6) δ 7.72 (bs, 1 H), 7.53 (m, 4H), 3.33 (s, 2 H), 2.16 (s, 3 H), 1.45 (s, 6 H).