(R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one → (R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one

HRID 2209058Notes

Reaction equation

HRID 2209058 reaction equation
[C:1]([N:5]1[CH:9]=[C:8]([C:10]2[N:15]=[C:14]([O:16][C@@H:17]([C@H:19]3[CH2:23][N:22]([C@@H](C4C=CC(OC)=CC=4)C)[C:21](=[O:34])[CH2:20]3)[CH3:18])[C:13]3[N:35]([CH:38]([F:40])[F:39])[CH:36]=[N:37][C:12]=3[CH:11]=2)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2]>C(O)(C(F)(F)F)=O>[C:1]([N:5]1[CH:9]=[C:8]([C:10]2[N:15]=[C:14]([O:16][C@@H:17]([C@H:19]3[CH2:23][NH:22][C:21](=[O:34])[CH2:20]3)[CH3:18])[C:13]3[N:35]([CH:38]([F:40])[F:39])[CH:36]=[N:37][C:12]=3[CH:11]=2)[CH:7]=[N:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

3

Reactant 1

HCID 117843539(R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Product 1

HCID 117842962(R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-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-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.34 (max. 0.107 mmol) was dissolved in TFA (2 mL) and heated to 60° C. with stirring. After 15 h, the red solution was concentrated in vacuo and diluted with EtOAc (20 mL) and 1:1 saturated aqueous NaHCO3: brine (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 silica gel. Purification by silica gel chromatography (40% to 100% acetone in hexanes) provided (R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.03.

Workup

  1. concentrationthe red solution was concentrated in vacuo
  2. additiondiluted with EtOAc (20 mL) and 1:1 saturated aqueous NaHCO3
  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 silica gel
  8. customPurification by silica gel chromatography (40% to 100% acetone in hexanes)

Sources & evidence

ORD record
ord-d5d22c3e15f549efaf508e748b8f9986
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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