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

HRID 2208993Notes

Reaction equation

HRID 2208993 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1.[OH:16][C@@H:17]([C@H:19]1[CH2:23][N:22]([C@@H:24]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[CH3:25])[C:21](=[O:34])[CH2:20]1)[CH3:18].[Cl:35][C:36]1[N:41]=[C:40](S(C)(=O)=O)[C:39]2[N:46]([CH3:49])[CH:47]=[N:48][C:38]=2[CH:37]=1>CN(C=O)C>[Cl:35][C:36]1[N:41]=[C:40]([O:16][C@@H:17]([C@H:19]2[CH2:23][N:22]([C@@H:24]([C:26]3[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=3)[CH3:25])[C:21](=[O:34])[CH2:20]2)[CH3:18])[C:39]2[N:46]([CH3:49])[CH:47]=[N:48][C:38]=2[CH:37]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 1178428886-chloro-3-methyl-4-(methylsulfonyl)-3H-imidazo[4,5-c]pyridineHCID 117843967(R)-4-((R)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Product 1

HCID 117843074(R)-4-((R)-1-(6-chloro-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 6228DimethylformamideSolvent2×

Procedure

A solution of NaHMDS in THF (1.0 M, 1.05 mL, 1.05 mmol) was added to a solution of (R)-4-((R)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.04 (277 mg, 1.05 mmol) in DMF (14 mL) at room temperature. After 18 minutes, a suspension of 6-chloro-3-methyl-4-(methylsulfonyl)-3H-imidazo[4,5-c]pyridine 2.04 (237 mg, 0.967 mmol) in DMF (4 mL) was added and mixture stirred at room temperature. After 40 minutes, LC/MS indicated full conversion to desired product. Reaction mixture was quenched with 15 mL of water, poured into 30 mL of water and extracted with ethyl acetate (3×50 mL). Combined organics were washed with 50% Brine (2×50 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure to a residue. This residue was purified by silica gel column chromatography (0-10% methanol in dichloromethane) to yield (R)-4-((R)-1-(6-chloro-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.05.

Workup

  1. additionwas added
  2. waitAfter 40 minutes

Sources & evidence

ORD record
ord-3d2a95bbb33d4f3cbddfbd585202391f
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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