Ammonium formate → 1-{[3-(4-methoxybenzyl)-2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one

HRID 1896463Notes

Reaction equation

HRID 1896463 reaction equation
[N+:1]([CH2:4][CH:5]([CH2:12][CH2:13][CH3:14])[CH2:6][C:7]([O:9]CC)=O)([O-])=O.C([O-])=O.[NH4+].[CH3:19][O:20][C:21]1[CH:44]=[CH:43][C:24]([CH2:25][N:26]2[C:30]3=[N:31][CH:32]=[CH:33][C:34]([CH:35]=O)=[C:29]3[N:28]=[C:27]2[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:23][CH:22]=1>CO.CCOCC.[Pd]>[CH3:19][O:20][C:21]1[CH:44]=[CH:43][C:24]([CH2:25][N:26]2[C:30]3=[N:31][CH:32]=[CH:33][C:34]([CH2:35][N:1]4[CH2:4][CH:5]([CH2:12][CH2:13][CH3:14])[CH2:6][C:7]4=[O:9])=[C:29]3[N:28]=[C:27]2[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[CH:23][CH:22]=1

Participants

7

Reactant 3

HCID 2723923Ammonium formateHCID 14463324Ethyl 3-(nitromethyl)hexanoateHCID 536291983-(4-methoxybenzyl)-2-phenyl-3H-imidazo[4,5-b]pyridine-7-carbaldehyde

Product 1

HCID 536291991-{[3-(4-methoxybenzyl)-2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-oneYield 68.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

Ethyl 3-(nitromethyl)hexanoate (0.52 g, 1.1 eq, 2.55 mmol) is dissolved in absolute methanol (8 ml). Then 10% Pd/C (0.2 g) and ammonium formate (1 g) are added under vigorous stirring. After 15 min, the mixture is diluted with ether (100 ml) and filtered. The solid on the filter is washed with ether (2×50 ml). A solution of 3-(4-methoxybenzyl)-2-phenyl-3H-imidazo[4,5-b]pyridine-7-carbaldehyde x225 (1 g, 1 eq, 2.9 mmol) in methanol (5 ml) is added immediately. The combined solution is evaporated in the vacuum of a rotary evaporator. The residue is dissolved in methanol (10 ml), CH(OMe)3 (0.5 ml) is added and the obtained solution is stirred at room temperature for 16 h. An excess of NaBH4 (1 g in several small portions) is then added under vigorous stirring for 20 min. The reaction mixture is evaporated in the vacuum of a rotary evaporator. The residue is partitioned between ethyl acetate and water. The organic phase is separated, dried with anhydrous sodium sulfate, and evaporated. The residue is dissolved in acetonitrile (10 ml), and the solution is refluxed for 24 h to complete the cyclization. The solvent is distilled off. The residue is purified by chromatography on silicagel (CCl4/MeCN) to yield 0.79 g of 1-{[3-(4-methoxybenzyl)-2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one x226.

Workup

  1. filtrationfiltered
  2. washThe solid on the filter is washed with ether (2×50 ml)
  3. customThe combined solution is evaporated in the vacuum of a rotary evaporator
  4. dissolutionThe residue is dissolved in methanol (10 ml)
  5. additionCH(OMe)3 (0.5 ml) is added
  6. additionAn excess of NaBH4 (1 g in several small portions) is then added
  7. stirringunder vigorous stirring for 20 min
  8. customThe reaction mixture is evaporated in the vacuum of a rotary evaporator
  9. customThe residue is partitioned between ethyl acetate and water
  10. customThe organic phase is separated
  11. dry with materialdried with anhydrous sodium sulfate
  12. customevaporated
  13. dissolutionThe residue is dissolved in acetonitrile (10 ml)
  14. temperaturethe solution is refluxed for 24 h
  15. distillationThe solvent is distilled off
  16. customThe residue is purified by chromatography on silicagel (CCl4/MeCN)

Sources & evidence

ORD record
ord-e582909b4b9a4cb89c612a57087c9c53
Source dataset
uspto-grants-2013_08
Patent number
US08518943B2

Reaction notes

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