Hydrochloric Acid → 3-(4-Piperidin-4-yl-phenyl)-1-pyridazin-4-yl-3-o-tolyl-propan-1-one dihydrochloride
Reaction equation
[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]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
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]+.
Workup
- concentrationafter 18 h the reaction mixture was concentrated in vacuo
Sources & evidence
- ORD record
- ord-9a850b9933b5418c9b41e9bbcfe1d2dc
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09090565B2
Reaction notes
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