Triethylamine → ethyl 4-({[6-{[bis(3-methylbutyl)amino]carbonyl}-1-(3-piperidin-1-ylpropyl)-1H-benzimidazol-2-yl]carbonyl}amino)benzoate hydrochloride

HRID 1516754Notes

Reaction equation

HRID 1516754 reaction equation
C(N(CC)CC)C.[Cl:8][CH2:9][C:10]([NH:12][C:13]1[CH:23]=[CH:22][C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][CH:14]=1)=[O:11].[S].[NH2:25][C:26]1[CH:44]=[CH:43][C:29]([C:30]([N:32]([CH2:38][CH2:39][CH:40]([CH3:42])[CH3:41])[CH2:33][CH2:34][CH:35]([CH3:37])[CH3:36])=[O:31])=[CH:28][C:27]=1[NH:45][CH2:46][CH2:47][CH2:48][N:49]1[CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]1>C(O)C>[ClH:8].[CH3:36][CH:35]([CH3:37])[CH2:34][CH2:33][N:32]([CH2:38][CH2:39][CH:40]([CH3:42])[CH3:41])[C:30]([C:29]1[CH:43]=[CH:44][C:26]2[N:25]=[C:9]([C:10]([NH:12][C:13]3[CH:23]=[CH:22][C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][CH:14]=3)=[O:11])[N:45]([CH2:46][CH2:47][CH2:48][N:49]3[CH2:50][CH2:51][CH2:52][CH2:53][CH2:54]3)[C:27]=2[CH:28]=1)=[O:31]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 244075Ethyl 4-[(chloroacetyl)amino]benzoateHCID 5362487SulfurHCID 684463484-amino-N,N-bis(3-methylbutyl)-3-[(3-piperidin-1-ylpropyl)amino]benzamide

Product 1

HCID 69654046ethyl 4-({[6-{[bis(3-methylbutyl)amino]carbonyl}-1-(3-piperidin-1-ylpropyl)-1H-benzimidazol-2-yl]carbonyl}amino)benzoate hydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
130 °C

Procedure

Triethylamine (100 μL), ethyl 4-[(chloroacetyl)amino]benzoate (173 mg) and sulphur (12 mg) are successively added to a solution of 4-amino-N,N-bis(3-methylbutyl)-3-[(3-piperidin-1-ylpropyl)amino]benzamide (100 mg) in ethanol (3 ml), placed in a “Personal Chemistry®” reaction tube. The tube is sealed with a cap, placed in the “Personal Chemistry®” microwave and heated under magnetic stirring at 130° C. for 20 minutes. The ethanol is then evaporated off and water and dichloromethane are added to the residue. After decantation and extraction, the combined organic phases are washed with salt water, dried over Na2SO4 then concentrated under reduced pressure at 40° C. Purification of the compound by flash chromatography on silica gel (eluent: 100% dichloromethane to dichloromethane/ethanol 85:15) produces the expected compound in the form of the free base. The corresponding hydrochloride salt is formed by the addition of a solution of 1N hydrochloric acid in diethyl ether. The precipitate obtained is filtered and dried in order to produce the expected monohydrochloride compound (80 mg, 51% yield).

Workup

  1. customplaced in a “Personal Chemistry®” reaction tube
  2. customThe tube is sealed with a cap
  3. temperatureheated
  4. customThe ethanol is then evaporated off
  5. additionwater and dichloromethane are added to the residue
  6. extractionAfter decantation and extraction
  7. washthe combined organic phases are washed with salt water
  8. dry with materialdried over Na2SO4
  9. concentrationthen concentrated under reduced pressure at 40° C
  10. customPurification of the compound by flash chromatography on silica gel (eluent: 100% dichloromethane to dichloromethane/ethanol 85:15)

Sources & evidence

ORD record
ord-853ef740bd834b9fbf3f499890eb601d
Source dataset
uspto-grants-2012_07
Patent number
US08227485B2

Reaction notes

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