Isoquinoline-4-boronic acid → 2-(1-hydroxyethyl)-1-[3-(isoquinolin-4-yl)phenyl]-5~[(4-methoxybenzyl)oxy]pyridin-4(1H)-one

HRID 1056902Notes

Reaction equation

HRID 1056902 reaction equation
[OH:1][CH:2]([C:4]1[N:5]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23](Br)[CH:22]=2)[CH:6]=[C:7]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[C:8](=[O:10])[CH:9]=1)[CH3:3].[CH:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31](B(O)O)=[CH:30][N:29]=1>>[OH:1][CH:2]([C:4]1[N:5]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:31]3[C:32]4[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:28]=[N:29][CH:30]=3)[CH:22]=2)[CH:6]=[C:7]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[C:8](=[O:10])[CH:9]=1)[CH3:3]

Participants

3

Reactant 2

HCID 3761204Isoquinoline-4-boronic acidHCID 674183731-(3-bromophenyl)-2-(1-hydroxyethyl)-5-[(4-methoxybenzyl)oxy]pyridin-4(1H)-one

Product 1

HCID 674192012-(1-hydroxyethyl)-1-[3-(isoquinolin-4-yl)phenyl]-5~[(4-methoxybenzyl)oxy]pyridin-4(1H)-one

Conditions

Temperature
80 °C

Procedure

To a 100 mL round-bottom flask were added 4.20 g (9.76 mmol) of 2-(1-hydroxyethyl)-1-[3-bromophenyl]-5-[(4-methoxybenzyl)oxy]pyridin-4(1H)-one, 3.38 g (19.52 mmol) isoquinolin-4-ylboronic acid, 0.75 g (0.97 mmol) 1,-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex. The flask was equipped with a condenser, evacuated, and purged with nitrogen. Evacuation was repeated three times and 50 mL THF and 40 mL 1 M aq cesium carbonate were added. The reaction mixture was heated at 80° C. for 3 h, Upon cooling, the organic layer was separated, washed with 15 mL water, dried over Na2S04 filtered, stirred over Quadrapure TU resin (Aldrich), concentrated in vacuo, and used without further purification, LCMS (M+H)+ 479.5.

Workup

  1. customThe flask was equipped with a condenser
  2. customevacuated
  3. custompurged with nitrogen
  4. additionwere added
  5. temperatureUpon cooling
  6. customthe organic layer was separated
  7. washwashed with 15 mL water
  8. customdried over Na2S04
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customused without further purification, LCMS (M+H)+ 479.5

Sources & evidence

ORD record
ord-cf1e8b060e57483e8e61a3a8c83a5017
Source dataset
uspto-grants-2016_07
Patent number
US09399651B2

Reaction notes

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