Water → (R)-3-[5-Cyano-1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yl]-3-phenyl-propionic acid ethyl ester

HRID 2175196Notes

Reaction equation

HRID 2175196 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C@@H:6]([N:13]1[C:17]2=[N:18][C:19]([C:22]#[N:23])=[CH:20][CH:21]=[C:16]2[NH:15][C:14]1=[O:24])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2].[I-].[CH3:27][N:28]1[C:36]2[C:31](=[C:32]([CH3:37])[CH:33]=[CH:34][CH:35]=2)[C:30]([CH2:38][N+](C)(C)C)=[CH:29]1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C@@H:6]([N:13]1[C:17]2=[N:18][C:19]([C:22]#[N:23])=[CH:20][CH:21]=[C:16]2[N:15]([CH2:38][C:30]2[C:31]3[C:36](=[CH:35][CH:34]=[CH:33][C:32]=3[CH3:37])[N:28]([CH3:27])[CH:29]=2)[C:14]1=[O:24])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 17836486((1,4-Dimethylindole-3-yl)methyl)trimethylammonium iodideHCID 58497426(R)-3-(5-Cyano-2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yl)-3-phenyl-propionic acid ethyl ester

Product 1

HCID 58497442(R)-3-[5-Cyano-1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yl]-3-phenyl-propionic acid ethyl esterYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-3-(5-cyano-2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yl)-3-phenyl-propionic acid ethyl ester (60 mg, 0.18 mmol) in DMF (5 ml) were added (1,4-dimethyl-1H-indol-3-ylmethyl)-trimethyl-ammonium iodide (74 mg, 0.21 mmol) and K2CO3 (30 mg, 0.21 mmol) at room temperature under nitrogen atmosphere. The solution was heated at 60° C. for 18 hours. The solution was cooled and poured into water and EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (1×). The combined organics were dried (MgSO4), filtered and concentrated. The remaining residue was purified via silica gel flash column chromatography (Companion, 12 g silica gel, 30-50% EtOAc/hexanes) to give 70 mg (80%) of the title compound as foam.

Workup

  1. temperatureThe solution was cooled
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc (1×)
  4. dry with materialThe combined organics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe remaining residue was purified via silica gel flash column chromatography (Companion, 12 g silica gel, 30-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e186a4b7514f44c389f44dca4932c86f
Source dataset
uspto-grants-2015_06
Patent number
US09062056B2

Reaction notes

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