Hydrochloric Acid → 3-(4-Piperidin-4-yl-phenyl)-1-pyridazin-4-yl-3-o-tolyl-propan-1-one dihydrochloride
反応式
[O:1]=[C:2]([C:31]1[CH:36]=[CH:35][N:34]=[N:33][CH:32]=1)[CH2:3][CH:4]([C:12]1[CH:17]=[CH:16][C:15]([CH:18]2[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]2)=[CH:14][CH:13]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH3:11].[ClH:37]>C(O)C>[ClH:37].[ClH:37].[NH:21]1[CH2:22][CH2:23][CH:18]([C:15]2[CH:14]=[CH:13][C:12]([CH:4]([C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[CH3:11])[CH2:3][C:2]([C:31]3[CH:36]=[CH:35][N:34]=[N:33][CH:32]=3)=[O:1])=[CH:17][CH:16]=2)[CH2:19][CH2:20]1参加物
4
実験手順
To a solution of tert-butyl 4-(4-(3-oxo-3-(pyridazin-4-yl)-1-o-tolylpropyl)phenyl)-piperidine-1-carboxylate (66 mg, 136 μmol) in ethanol (1.5 mL) was added hydrogen chloride solution (4 M in 1,4-dioxane, 0.34 mL, 1.36 mmol), then after 18 h the reaction mixture was concentrated in vacuo to produce 3-(4-piperidin-4-yl-phenyl)-1-pyridazin-4-yl-3-o-tolyl-propan-1-one dihydrochloride (63 mg, light brown foam, MS: 386.4 [M+H]+). This was dissolved in dichloromethane (2.5 mL), then after addition of N,N-diisopropylethylamine (87.8 mg, 680 μmol) the reaction mixture was cooled to 0° C. and treated with methanesulfonyl chloride (31.1 mg, 272 μmol) was added. After 30 min the reaction mixture was partitioned between sat. aq. ammonium chloride solution and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate, filtered and evaporated. Chromatography (SiO2; gradient dichloromethane to dichloromethane/methanol/25% aq. ammonia solution 95:5:0.25) afforded the title compound (45 mg, 71%). Light yellow foam; MS: 464.2 [M+H]+.