Acetic Acid → N-((4-(4-(pyridin-4-yl)-piperazin-1-yl)piperidin-4-yl)methyl)acetamide
Reaction equation
C([N:8]1[CH2:13][CH2:12][C:11]([CH2:26][NH:27][C:28](=[O:30])[CH3:29])([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)[CH2:10][CH2:9]1)C1C=CC=CC=1.CC(O)=O>CO.[OH-].[OH-].[Pd+2]>[N:23]1[CH:24]=[CH:25][C:20]([N:17]2[CH2:16][CH2:15][N:14]([C:11]3([CH2:26][NH:27][C:28](=[O:30])[CH3:29])[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[CH2:19][CH2:18]2)=[CH:21][CH:22]=1Participants
Procedure
A degassed solution containing N-((1-benzyl-4-(4-(pyridin-4-yl)piperazin-1-yl)piperidin-4-yl)methyl)acetamide AM14 (1.96 mmol), AcOH (0.3 ml) and Pd(OH)2 in methanol was hydrogenated for 16 h to yield N-((4-(4-(pyridin-4-yl)-piperazin-1-yl)piperidin-4-yl)methyl)acetamide AM2, which was obtained after passage through a celite pad and solvent removed under reduced pressure. N-((4-(4-(pyridin-4-yl)piperazin-1-yl)piperidin-4-yl)methyl)acetamide AM2 was re-dissolved in dichloromethane and added to a solution containing 2-(2-(N-cyclopropyl-4-methoxy-2,6-dimethylphenylsulfonamido)ethoxy)acetic acid AC7 (0.8 equiv.), EDCI (1.5 equiv.), HOBT (1 equiv.) and DIPEA (4 equiv.) in dichloromethane at 0° C. The reaction mixture was warmed to room temperature and stirred for 16 h. The mixture was diluted with dichloromethane and was given aq. NH4Cl and aq. NaHCO3 washes. The organic layer was dried over sodium sulfate and the solvent removed. The crude product was purified by alumina column chromatography. Yield: 5%. MS, Rt=2.5 min, m/z=657.5 [MH]+.
Sources & evidence
- ORD record
- ord-bc1594668d5e4fbab461da06b097fa64
- Source dataset
- uspto-grants-2013_09
- Patent number
- US08541573B2
Reaction notes
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