1,2-Dimethoxyethane → (R)-4-((R)-1-(3-methyl-6-(4-(piperazin-1-yl)phenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one

HRID 2209046Notes

Reaction equation

HRID 2209046 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][C@@H:9]([C@H:11]2[CH2:15][NH:14][C:13](=[O:16])[CH2:12]2)[CH3:10])[C:5]2[N:17]([CH3:20])[CH:18]=[N:19][C:4]=2[CH:3]=1.O[C@@H]([C@H]1CN([C@@H]([C:31]2[CH:36]=[CH:35][C:34](OC)=[CH:33][CH:32]=2)C)C(=O)C1)C.B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].CO[CH2:51][CH2:52]OC>O>[CH3:20][N:17]1[C:5]2[C:6]([O:8][C@@H:9]([C@H:11]3[CH2:15][NH:14][C:13](=[O:16])[CH2:12]3)[CH3:10])=[N:7][C:2]([C:31]3[CH:32]=[CH:33][C:34]([N:7]4[CH2:52][CH2:51][NH:17][CH2:5][CH2:6]4)=[CH:35][CH:36]=3)=[CH:3][C:4]=2[N:19]=[CH:18]1

Participants

7

Reactant 5

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 61668Boronic AcidHCID 117843294(R)-4-((R)-1-((6-chloro-3-methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-oneHCID 117843967(R)-4-((R)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Product 1

HCID 117844142(R)-4-((R)-1-(3-methyl-6-(4-(piperazin-1-yl)phenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To an appropriate sized container charged with a magnetic stir bar, aryl halide 2.06, 2.58 or 2.62 (1 equiv), boronic acid or ester (1.2 equiv), cesium carbonate (3 equiv), and PEPPSI-IPr catalyst (0.1 equiv) were added and reagents were taken up in 2:1 DME:water. After evacuating and backfilling with argon, mixture was heated at 100° C. for one hour. After cooling to room temperature, mixture is poured into water and extracted with ethyl acetate. Combined organics were dried, filtered, and concentrated under reduced pressure and resulting residues were purified by silica gel column chromatography or reverse phase HPLC to yield Examples 3B.01-3B.31.

Workup

  1. additionTo an appropriate sized container charged with a magnetic stir bar
  2. customAfter evacuating
  3. temperatureAfter cooling to room temperature
  4. additionmixture is poured into water
  5. extractionextracted with ethyl acetate
  6. customCombined organics were dried
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customresulting residues
  10. customwere purified by silica gel column chromatography
  11. customto yield Examples 3B.01-3B.31

Sources & evidence

ORD record
ord-9152d15721ab47f2b83dc397703c2a28
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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