4-Methoxyphenylacetyl chloride → 2-(4-methoxybenzyl)-N,N-bis(3-methylbutyl)-1-(3-piperidin-1-ylpropyl)-1H-benzimidazole-6-carboxamide hydrochloride

HRID 1516752Notes

Reaction equation

HRID 1516752 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([Cl:12])=O)=[CH:5][CH:4]=1.[NH2:13][C:14]1[CH:32]=[CH:31][C:17]([C:18]([N:20]([CH2:26][CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])=[O:19])=[CH:16][C:15]=1[NH:33][CH2:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1>CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O.ClCCl>[ClH:12].[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][C:10]2[N:33]([CH2:34][CH2:35][CH2:36][N:37]3[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42]3)[C:15]3[CH:16]=[C:17]([C:18]([N:20]([CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:26][CH2:27][CH:28]([CH3:30])[CH3:29])=[O:19])[CH:31]=[CH:32][C:14]=3[N:13]=2)=[CH:7][CH:8]=1

Participants

5

Reactant 2

HCID 27346884-Methoxyphenylacetyl chlorideHCID 684463484-amino-N,N-bis(3-methylbutyl)-3-[(3-piperidin-1-ylpropyl)amino]benzamide

Product 1

HCID 696538992-(4-methoxybenzyl)-N,N-bis(3-methylbutyl)-1-(3-piperidin-1-ylpropyl)-1H-benzimidazole-6-carboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterSolvent

Conditions

Temperature
100 °C

Procedure

4-methoxyphenylacetylchloride (32 mg, 1.1 eq) is added to a solution of 4-amino-N,N-bis(3-methylbutyl)-3-[(3-piperidin-1-ylpropyl)amino]benzamide (66 mg) in acid acetic (2 ml). The mixture is heated at 100° C. for 18 hours then cooled down and concentrated under reduced pressure. A saturated aqueous solution of sodium hydrogen carbonate is added to the residue obtained dissolved in dichloromethane. After decantation and extractions, the combined organic phases are washed with salt water, dried over Na2SO4 and concentrated under reduced pressure. Purification of the residue obtained by flash chromatography on silica gel (eluent: 100% dichloromethane to dichloromethane/methanol 9:1) produces the expected compound in the form of the free base. The corresponding hydrochloride salt is formed by the addition of a 1N solution of hydrochloric acid in diethyl ether. The precipitate obtained is filtered and dried in order to produce the expected monohydrochloride compound (51 mg, 59% yield).

Workup

  1. temperaturethen cooled down
  2. concentrationconcentrated under reduced pressure
  3. additionA saturated aqueous solution of sodium hydrogen carbonate is added to the residue
  4. customobtained
  5. extractionAfter decantation and extractions
  6. washthe combined organic phases are washed with salt water
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customPurification of the residue
  10. customobtained by flash chromatography on silica gel (eluent: 100% dichloromethane to dichloromethane/methanol 9:1)

Sources & evidence

ORD record
ord-dc8f8a60a6d9436980ac65b1e5cad7cf
Source dataset
uspto-grants-2012_07
Patent number
US08227485B2

Reaction notes

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