Sodium Bicarbonate → 1-ethyl-3-[1-(1-methyl-1H-benzimidazol-2-yl)-2,3-dihydro-1H-indol-5-yl]-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 1429923Notes

Reaction equation

HRID 1429923 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([N:10]3[C:14]4=[N:15][CH:16]=[CH:17][CH:18]=[C:13]4[N:12]([CH2:19][CH3:20])[C:11]3=[O:21])=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.Cl[C:23]1[N:27]([CH2:28]OCC[Si](C)(C)C)[C:26]2[CH:36]=[CH:37][CH:38]=[CH:39][C:25]=2[N:24]=1.C([O-])(O)=O.[Na+]>CN1C(=O)CCC1>[CH2:19]([N:12]1[C:13]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[N:10]([C:6]2[CH:5]=[C:4]3[C:9](=[CH:8][CH:7]=2)[N:1]([C:23]2[N:27]([CH3:28])[C:26]4[CH:36]=[CH:37][CH:38]=[CH:39][C:25]=4[N:24]=2)[CH2:2][CH2:3]3)[C:11]1=[O:21])[CH3:20]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 585772823-(2,3-dihydro-1H-indol-5-yl)-1-ethyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneHCID 597528982-Chloro-1-[[2-(trimethylsilanyl)ethoxy]methyl]-benzimidazole

Product 1

HCID 585776601-ethyl-3-[1-(1-methyl-1H-benzimidazol-2-yl)-2,3-dihydro-1H-indol-5-yl]-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneYield 8.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-(2,3-dihydro-1H-indol-5-yl)-1-ethyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (100 mg) and 2-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole (101 mg) in NMP (2 mL) was stirred at 120° C. for 10 h, treated with saturated NaHCO3 solution and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was dissolved in DMF (2 mL), and then iodomethane (0.022 mL) and Cs2CO3 (0.176 g) were added. The mixture was stirred at room temperature for 3 h, treated with water and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was suspended in CH3CN and the precipitate was filtered off. The residue was purified by prep. HPLC, and then chromatographed on silica gel eluting with AcOEt/Hexane. Crystallization from AcOEt/Hexane gave the title compound (12 mg).

Workup

  1. extractionextracted with AcOEt
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in DMF (2 mL)
  5. additioniodomethane (0.022 mL) and Cs2CO3 (0.176 g) were added
  6. stirringThe mixture was stirred at room temperature for 3 h
  7. additiontreated with water
  8. extractionextracted with AcOEt
  9. dry with materialThe organic layer was dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. filtrationthe precipitate was filtered off
  12. customThe residue was purified by prep
  13. customHPLC, and then chromatographed on silica gel eluting with AcOEt/Hexane
  14. customCrystallization from AcOEt/Hexane

Sources & evidence

ORD record
ord-7cecc9dfb08c4221b5f61891a7e3c773
Source dataset
uspto-grants-2015_01
Patent number
US08940758B2

Reaction notes

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