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

HRID 2209057Notes

Reaction equation

HRID 2209057 reaction equation
[F:1][CH:2]([F:41])[N:3]1[C:7]2[C:8]([O:22][C@@H:23]([C@H:25]3[CH2:29][N:28]([C@@H](C4C=CC(OC)=CC=4)C)[C:27](=[O:40])[CH2:26]3)[CH3:24])=[N:9][C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)=[CH:11][C:6]=2[N:5]=[CH:4]1>C(O)(C(F)(F)F)=O>[F:41][CH:2]([F:1])[N:3]1[C:7]2[C:8]([O:22][C@@H:23]([C@H:25]3[CH2:29][NH:28][C:27](=[O:40])[CH2:26]3)[CH3:24])=[N:9][C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)=[CH:11][C:6]=2[N:5]=[CH:4]1

Participants

3

Reactant 1

HCID 117843944(R)-4-((R)-1-(3-(difluoromethyl)-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 117843350(R)-4-((R)-1-(3-(difluoromethyl)-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-(difluoromethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.30 (max. 0.153 mmol) was dissolved in TFA (2 mL) and heated to 60° C. with stirring. After 22 h, the red solution was concentrated in vacuo and diluted with EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL). The phases were separated and the aqueous phase was extracted with EtOAc (20 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated onto 2 g silica gel. Purification by silica gel chromatography (0% to 2.5% to 5% MeOH in DCM) provided (R)-4-((R)-1-(3-(difluoromethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.02.

Workup

  1. concentrationthe red solution was concentrated in vacuo
  2. additiondiluted with EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with EtOAc (20 mL)
  5. dry with materialThe combined organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated onto 2 g silica gel
  8. customPurification by silica gel chromatography (0% to 2.5% to 5% MeOH in DCM)

Sources & evidence

ORD record
ord-830cbdbe8d5a44aca1ae03fb36c662d1
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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