Ethyl Acetate → 5-[(diisobutylamino)methyl]-1-(3-{methyl[2-(2-pyridinyl)ethyl]amino}propyl)-N-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-2-amine

HRID 883695Notes

Reaction equation

HRID 883695 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:11]([CH2:49][CH:50]([CH3:52])[CH3:51])[C:12]([C:14]1[CH:48]=[CH:47][C:17]2[N:18]([CH2:34][CH2:35][CH2:36][N:37]([CH3:46])[CH2:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=3)[C:19]([NH:21][C:22]3[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([O:32][CH3:33])[CH:23]=3)=[N:20][C:16]=2[CH:15]=1)=O)[CH:8]([CH3:10])[CH3:9].C(OCC)(=O)C>O1CCCC1>[CH2:7]([N:11]([CH2:12][C:14]1[CH:48]=[CH:47][C:17]2[N:18]([CH2:34][CH2:35][CH2:36][N:37]([CH3:46])[CH2:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=3)[C:19]([NH:21][C:22]3[CH:23]=[C:24]([O:32][CH3:33])[C:25]([O:30][CH3:31])=[C:26]([O:28][CH3:29])[CH:27]=3)=[N:20][C:16]=2[CH:15]=1)[CH2:49][CH:50]([CH3:51])[CH3:52])[CH:8]([CH3:10])[CH3:9]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 10196994N,N-diisobutyl-1-{3-[methyl(2-pyridin-2-ylethyl)amino]propyl}-2-[(3,4,5-trimethoxyphenyl)amino]-1H-benzimidazole-5-carboxamideHCID 21226445Aluminium lithium hydride

Product 1

HCID 575676335-[(diisobutylamino)methyl]-1-(3-{methyl[2-(2-pyridinyl)ethyl]amino}propyl)-N-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-2-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A molar solution of lithium aluminium hydride in tetrahydrofuran (0.83 ml, 5 eq) is added dropwise to a solution of N,N-diisobutyl-1-{3-[methyl(2-pyridin-2-ylethyl)amino]propyl}-2-[(3,4,5-trimethoxyphenyl)amino]-1H-benzimidazole-5-carboxamide (105 mg, 1 eq. prepared according to Example A1) cooled down to 0° C., in tetrahydrofuran (3 ml). After stirring for 15 minutes at 0° C., the mixture is heated at 60° C. for 3 hours then cooled down to 0° C. and hydrolysed. After adding ethyl acetate, decanting and extraction, the combined organic phases are washed with salt water, followed by drying over sodium sulphate and concentrating under reduced pressure. Purification by flash chromatography on silica gel (eluent: 100% dichloromethane to dichloromethane/methanol 9:1) produces the expected compound in the form of a foam (63 mg, 62% yield).

Workup

  1. temperaturethe mixture is heated at 60° C. for 3 hours
  2. temperaturethen cooled down to 0° C.
  3. customdecanting
  4. extractionextraction
  5. washthe combined organic phases are washed with salt water
  6. dry with materialby drying over sodium sulphate
  7. concentrationconcentrating under reduced pressure
  8. customPurification by flash chromatography on silica gel (eluent: 100% dichloromethane to dichloromethane/methanol 9:1)

Sources & evidence

ORD record
ord-72833a29858e45b6b3760219c6392be7
Source dataset
uspto-grants-2012_08
Patent number
US08236965B2

Reaction notes

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