Oxalyl chloride → N-{2-[2-(4-diphenylmethyl-piperazin-1-yl)-ethoxy]-ethyl}-3-pyridin-3-yl-acrylamide trihydrochloride

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]=[CH:8][C:9]([OH:11])=O)[CH:2]=1.C(Cl)(=O)C([Cl:15])=O.[C:18]1([CH:24]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[N:25]2[CH2:30][CH2:29][N:28]([CH2:31][CH2:32][O:33][CH2:34][CH2:35][NH2:36])[CH2:27][CH2:26]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[ClH:15].[ClH:15].[ClH:15].[C:37]1([CH:24]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:25]2[CH2:26][CH2:27][N:28]([CH2:31][CH2:32][O:33][CH2:34][CH2:35][NH:36][C:9](=[O:11])[CH:8]=[CH:7][C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[CH2:29][CH2:30]2)[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

Reactant 3

HCID 65578Oxalyl chloride

HCID 1019843-(3-Pyridinyl)-2-propenoic acid

HCID 223976322-[2-(4-Diphenylmethyl-piperazin-1-yl)-ethoxy]-ethylamine

Product 1

HCID 69687141N-{2-[2-(4-diphenylmethyl-piperazin-1-yl)-ethoxy]-ethyl}-3-pyridin-3-yl-acrylamide trihydrochloride

Procedure

Batch size: 6.0 g (40 mmol) 3-(3-pyridyl)-acrylic acid, 9.4 ml (110 mmol) oxalyl chloride and 12.4 g (36.5 mmol) 2-[2-(4-diphenylmethyl-piperazin-1-yl)-ethoxy]-ethylamine. The crude product is chromatographically pre-purified over silica gel with CHCl3/CH3OH (98/2 to 95/5). After removal of the solvent, the residue is dissolved in isopropanol and mixed with isopropanolic HCl solution. The mixture is rotated in and the HCl salt is cyrstallized from 50 ml methanol/6 drops diisopropyl ether: Colorless crystals of MP. 157-159° C.; yield 0.6 g (3%).