Diisopropylethylamine → 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(4-fluorobenzyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dichlorophenyl)piperidine

HRID 323285Notes

Reaction equation

HRID 323285 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([O:34][CH3:35])[C:31]=1[O:32][CH3:33])[C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=2)([CH2:14][CH2:15]OS(C)(=O)=O)[CH2:9]1)=[O:7].[F:36][C:37]1[CH:59]=[CH:58][C:40]([CH2:41][N:42]2[C:46]3[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=3[N:44]=[C:43]2[NH:51][CH:52]2[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]2)=[CH:39][CH:38]=1.C(N(CC)C(C)C)(C)C.CO.C(OCC)(=O)C>C(#N)C>[CH3:35][O:34][C:30]1[CH:29]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:31]=1[O:32][CH3:33])[C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([CH2:14][CH2:15][N:55]2[CH2:56][CH2:57][CH:52]([NH:51][C:43]3[N:42]([CH2:41][C:40]4[CH:58]=[CH:59][C:37]([F:36])=[CH:38][CH:39]=4)[C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=4[N:44]=3)[CH2:53][CH2:54]2)([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=2)[CH2:9]1)=[O:7]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 123618TecastemizoleHCID 184647841-(3,4,5-Trimethoxybenzoyl)-3-(3,4-dichlorophenyl)-3-(2-methanesulfonyloxyethyl)piperidineHCID 21584119Ethylacetate methanol

Product 1

HCID 99623031-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(4-fluorobenzyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dichlorophenyl)piperidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(3,4-dichlorophenyl)-3-(2-methanesulfonyloxyethyl)piperidine (1.14 mmol) and (1-(4-fluorobenzyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amine (0.56 g, 1.7 mmol), and N,N-diisopropylethylamine (0.50 g) in acetonitrile (12 mL). Heat to reflux. After 2 days, partition the residue between ethyl acetate and water. Separate the organic layer and extract twice with saturated aqueous sodium bicarbonate solution and brine. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 30/70/0.33 methanol/ethyl acetate/concentrated aqueous ammonia to give the title compound: Rf=0.50 (silica gel, 30% methanol/ethyl acetate).

Workup

  1. temperatureHeat to reflux
  2. custompartition the residue between ethyl acetate and water
  3. customSeparate the organic layer
  4. extractionextract twice with saturated aqueous sodium bicarbonate solution and brine
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customto obtain a residue

Sources & evidence

ORD record
ord-a0e2a43ec20d4165a87be5e6b1e45fdd
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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