4,6-dichloro-2,3-dimethyl-3H-imidazo[4,5-c]pyridine → (R)-4-((R)-1-(6-chloro-2,3-dimethyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2209017Notes

Reaction equation

C(O[K])(C)(C)C.[OH:7][C@@H:8]([C@H:10]1[CH2:14][N:13]([C@@H:15]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH3:16])[C:12](=[O:25])[CH2:11]1)[CH3:9].Cl[C:27]1[C:32]2[N:33]([CH3:37])[C:34]([CH3:36])=[N:35][C:31]=2[CH:30]=[C:29]([Cl:38])[N:28]=1>C1COCC1>[Cl:38][C:29]1[N:28]=[C:27]([O:7][C@@H:8]([C@H:10]2[CH2:14][N:13]([C@@H:15]([C:17]3[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=3)[CH3:16])[C:12](=[O:25])[CH2:11]2)[CH3:9])[C:32]2[N:33]([CH3:37])[C:34]([CH3:36])=[N:35][C:31]=2[CH:30]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of tBuOK in THF (1.0 M, 0.92 mL, 0.92 mmol) was added to a solution of (R)-4-((R)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.04 (128 mg, 0.486 mmol) in THF (3 mL) at room temperature. After eighteen minutes, a suspension of 4,6-dichloro-2,3-dimethyl-3H-imidazo[4,5-c]pyridine 2.47 (0.1 g, 0.463 mmol) in THF (3 mL) was added and mixture stirred at 60° C. for fifteen minutes. LC/MS indicated full conversion to desired product. Reaction mixture was quenched with water, and extracted with ethyl acetate. Organic phase was dried over MgSO4 and evaporated under reduced pressure to obtain (R)-4-((R)-1-(6-chloro-2,3-dimethyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.48 that was used without further purification.

Workup

waitAfter eighteen minutes
additionwas added

Sources & evidence

ORD record: ord-0329f45d9dd84b0db8ef965d14de1d73
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376441B2

Reaction notes

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