Diisopropylethylamine → 4-{5-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine-1-ylmethyl]imidazol-1-ylmethyl}benzonitrile hydrochloride salt

HRID 443259Notes

Reaction equation

HRID 443259 reaction equation
Cl.[CH3:2][C:3]1[CH:4]=[C:5]([CH:16]=[CH:17][CH:18]=1)[CH2:6][C:7]1([CH2:13][O:14][CH3:15])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.Cl.[C:20]([C:22]1[CH:35]=[CH:34][C:25]([CH2:26][N:27]2[C:31]([CH2:32][Cl:33])=[CH:30][N:29]=[CH:28]2)=[CH:24][CH:23]=1)#[N:21].C(N(C(C)C)CC)(C)C>C(#N)C>[ClH:33].[CH3:15][O:14][CH2:13][C:7]1([CH2:6][C:5]2[CH:16]=[CH:17][CH:18]=[C:3]([CH3:2])[CH:4]=2)[CH2:12][CH2:11][N:10]([CH2:32][C:31]2[N:27]([CH2:26][C:25]3[CH:34]=[CH:35][C:22]([C:20]#[N:21])=[CH:23][CH:24]=3)[CH:28]=[N:29][CH:30]=2)[CH2:9][CH2:8]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 97953574-((5-(Chloromethyl)-1H-imidazol-1-yl)methyl)benzonitrile hydrochlorideHCID 211932194-(3-Methylbenzyl)-4-methoxymethylpiperidine hydrochloride salt

Product 1

HCID 211933614-{5-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine-1-ylmethyl]imidazol-1-ylmethyl}benzonitrile hydrochloride salt

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 4-(3-methylbenzyl)-4-methoxymethylpiperidine hydrochloride salt (1.57 g, 5.8 mmol), 1-(4-cyanobenzyl)-5-chloromethyl-imidazole hydrochloride salt (1.57 g, 5.8 mmol), and diisopropylethyl-amine (5.1 mL, 29 mmol) in anhydrous acetonitrile (75 mL) was heated at 60° C. overnight. The resultant mixture was concentrated under vacuum, and the residue was partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 3% methanol in chloroform. Collection and concentration of appropriate fractions provided the title compound as free base. The free base obtained was dissolved in anhydrous diethyl ether (50 mL), cooled to 0° C., and bubbled with anhydrous hydrogen chloride gas for 20 second. The resultant mixture was concentrated, and the residue solid recrystallized from a mixture of methanol and diethyl ether. The white solid precipitated was filtered, and residual solvent was removed under vacuum overnight to provide the title compound.

Workup

  1. concentrationThe resultant mixture was concentrated under vacuum
  2. customthe residue was partitioned between saturated aqueous sodium bicarbonate and dichloromethane
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-2feb44ef80004c609870c6b6bf7ec672
Source dataset
uspto-grants-1999_04
Patent number
US05891889

Reaction notes

Loading…