(R)-4-((R)-1-(3-cyclopropyl-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one → (R)-4-((R)-1-(3-cyclopropyl-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one

HRID 2209059Notes

Reaction equation

HRID 2209059 reaction equation
[CH:1]1([N:4]2[C:8]3[C:9]([O:23][C@@H:24]([C@H:26]4[CH2:30][N:29]([C@@H](C5C=CC(OC)=CC=5)C)[C:28](=[O:41])[CH2:27]4)[CH3:25])=[N:10][C:11]([C:13]4[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1>C(O)(C(F)(F)F)=O>[CH:1]1([N:4]2[C:8]3[C:9]([O:23][C@@H:24]([C@H:26]4[CH2:30][NH:29][C:28](=[O:41])[CH2:27]4)[CH3:25])=[N:10][C:11]([C:13]4[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1

Participants

3

Reactant 1

HCID 117843185(R)-4-((R)-1-(3-cyclopropyl-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Product 1

HCID 117843417(R)-4-((R)-1-(3-cyclopropyl-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
60 °C

Procedure

(R)-4-((R)-1-(3-cyclopropyl-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.38 (80 mg, 0.14 mmol) was dissolved in TFA (2 mL) and heated to 60° C. with stirring. After 1.75 h, the temperature was increased to 65° C. After an additional 4.25 h, the temperature was decreased to 55° C. After an additional 18 h, the red solution was concentrated in vacuo and diluted with EtOAc (15 mL) and saturated aqueous NaHCO3 (15 mL). The phases were separated and the aqueous phase was extracted with EtOAc (2×15 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated onto silica gel. Purification by silica gel chromatography (0% to 10% MeOH in DCM) provided (R)-4-((R)-1-(3-cyclopropyl-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.04

Workup

  1. temperaturethe temperature was increased to 65° C
  2. waitAfter an additional 4.25 h
  3. customwas decreased to 55° C
  4. waitAfter an additional 18 h
  5. concentrationthe red solution was concentrated in vacuo
  6. additiondiluted with EtOAc (15 mL) and saturated aqueous NaHCO3 (15 mL)
  7. customThe phases were separated
  8. extractionthe aqueous phase was extracted with EtOAc (2×15 mL)
  9. dry with materialThe combined organic phase was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated onto silica gel
  12. customPurification by silica gel chromatography (0% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-4ad0009a31484614b78dcc6613d7b6cf
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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