Sodium Bicarbonate → Ethyl 4-[4-chloro-2-[(2,6-dimethoxypyridin-3-yl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

HRID 1398768Notes

Reaction equation

HRID 1398768 reaction equation
Cl[C:2]1[N:6]([CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]2[C:15]([CH:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[CH:16][CH:17]=[C:18]([Cl:19])[C:4]=2[N:3]=1.Cl.[CH3:26][O:27][C:28]1[C:33]([NH2:34])=[CH:32][CH:31]=[C:30]([O:35][CH3:36])[N:29]=1.C(=O)(O)[O-].[Na+]>CN1CCCC1=O>[Cl:19][C:18]1[C:4]2[N:3]=[C:2]([NH:34][C:33]3[C:28]([O:27][CH3:26])=[N:29][C:30]([O:35][CH3:36])=[CH:31][CH:32]=3)[N:6]([CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]=2[C:15]([CH:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 27238812,6-Dimethoxypyridin-3-amine monohydrochlorideHCID 68761768Ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

Product 1

HCID 68763493Ethyl 4-[4-chloro-2-[(2,6-dimethoxypyridin-3-yl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoateYield 20.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 33; 500 mg, 1.35 mmol) and 2,6-dimethoxypyridin-3-amine monohydrochloride (768 mg, 4.04 mmol) in 1-methyl-2-pyrrolidinone (4 mL) was irradiated by microwave at 180° C. for 15 min. After cooling, aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. Organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 5-20% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound (133 mg, 0.272 mmol, 20%) as a colorless amorphous.

Workup

  1. customwas irradiated by microwave at 180° C. for 15 min
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washOrganic layer was washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel eluting with a 5-20% ethyl acetate/n-hexane gradient mixture
  8. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-3a1845b7535f4d588818c0af6397632b
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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