5-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-[tri(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine → 1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]-2-(1-hydroxyethyl)-5-[(4-methoxybenzyl)oxy]pyridin-4(1H)-one

HRID 571075Notes

Reaction equation

HRID 571075 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[CH:13]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11](=[O:24])[CH:10]=[C:9]2[CH:25]([OH:27])[CH3:26])[CH:5]=[CH:6][CH:7]=1.[Cl:28][C:29]1[C:30](B2OC(C)(C)C(C)(C)O2)=[C:31]2[CH:37]=[CH:36][N:35]([Si](C(C)C)(C(C)C)C(C)C)[C:32]2=[N:33][CH:34]=1>>[Cl:28][C:29]1[C:30]([C:2]2[CH:3]=[C:4]([N:8]3[CH:13]=[C:12]([O:14][CH2:15][C:16]4[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=4)[C:11](=[O:24])[CH:10]=[C:9]3[CH:25]([OH:27])[CH3:26])[CH:5]=[CH:6][CH:7]=2)=[C:31]2[CH:37]=[CH:36][NH:35][C:32]2=[N:33][CH:34]=1

Participants

3

Reactant 2

HCID 453617775-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-[tri(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridineHCID 674183731-(3-bromophenyl)-2-(1-hydroxyethyl)-5-[(4-methoxybenzyl)oxy]pyridin-4(1H)-one

Product 1

HCID 866802781-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]-2-(1-hydroxyethyl)-5-[(4-methoxybenzyl)oxy]pyridin-4(1H)-one

Conditions

Temperature
85 °C

Procedure

To a 250 mL round-bottom flask were added 2.25 g (5.23 mmol) of the first eluting enantiomer of 1-(3-bromophenyl)-2-(1-hydroxyethyl)-5-[(4-methoxybenzyl)oxy]pyridin-4(1H)-one, 4.55 g (10.46 mmol) 5-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine, and 0.427 g (0.523 mmol) 1,1′-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 THE and 25 mL 1 M aq cesium carbonate were added. The reaction mixture was heated at 85° C. for 15 h. Upon cooling, the organic layer was separated, washed with 10 mL water, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by flash chromatography (silica gel, 0-100% hexane-ethyl acetate gradient, followed by 10% methanol wash) afforded 1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]-2-(1-hydroxyethyl)-5-[(4-methoxybenzyl)oxy]pyridin-4(1H)-one. LCMS (M+H)+ 502.4.

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 10 mL water
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification
  12. washby flash chromatography (silica gel, 0-100% hexane-ethyl acetate gradient, followed by 10% methanol wash)

Sources & evidence

ORD record
ord-e71d7185dbff4280abfe192ec3acb10b
Source dataset
uspto-grants-2015_05
Patent number
US09024032B2

Reaction notes

Loading…