Potassium tert-butoxide → (R)-4-((R)-1-(6-bromo-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2209028Notes

Reaction equation

HRID 2209028 reaction equation
[OH:1][C@@H:2]([C@H:4]1[CH2:8][N:7]([C@@H:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH3:10])[C:6](=[O:19])[CH2:5]1)[CH3:3].CC(C)([O-])C.[K+].[Br:26][C:27]1[N:32]=[C:31](Cl)[C:30]2[N:34]([CH3:37])[CH:35]=[N:36][C:29]=2[CH:28]=1>C1COCC1>[Br:26][C:27]1[N:32]=[C:31]([O:1][C@@H:2]([C@H:4]2[CH2:8][N:7]([C@@H:9]([C:11]3[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=3)[CH3:10])[C:6](=[O:19])[CH2:5]2)[CH3:3])[C:30]2[N:34]([CH3:37])[CH:35]=[N:36][C:29]=2[CH:28]=1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 1178435766-Bromo-4-chloro-3-methyl-imidazo[4,5-c]pyridineHCID 117843967(R)-4-((R)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Product 1

HCID 117842978(R)-4-((R)-1-(6-bromo-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-4-((R)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.04 (135 mg, 0.51 mmol) in dry THF (6 mL) was added potassium tert-butoxide (72 mg, 0.64 mmol) and the reaction mixture was stirred at rt for 5 min. Then 6-bromo-4-chloro-3-methyl-3H-imidazo[4,5-c]pyridine 2.60 (105 mg, 0.43 mmol) was added and reaction mixture was heated to 60° C. After 12 h, cooled to rt, quenched the reaction mixture with water (0.5 mL) and concentrated. The residue was purified by flash column chromatography (SiO2, 0% MeOH/EtOAc to 20% EtOAc/hexanes) to give ((R)-4-((R)-1-(6-bromo-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.61.

Workup

  1. customreaction mixture
  2. temperaturewas heated to 60° C
  3. waitAfter 12 h
  4. temperaturecooled to rt
  5. customquenched the reaction mixture with water (0.5 mL)
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (SiO2, 0% MeOH/EtOAc to 20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e11f5d3856324143911ed47ec9bae6c8
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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