Potassium Carbonate → 8-(6-Fluoropyridin-3-yl)-3-methyl-1-(oxan-4-yl)imidazo[5,4-c]quinolin-2-one

HRID 1486912Notes

Reaction equation

HRID 1486912 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:22])[C:13](=[O:21])[N:14]([CH:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:5]=3[C:4]=2[CH:3]=1.[F:23][C:24]1[N:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.[Cl-].[Cl-].[Cl-].[Cl-].[Na].[Na].[Pd+4].C(P(C(C)(C)C)CCCS(O)(=O)=O)(C)(C)C>[F:23][C:24]1[N:29]=[CH:28][C:27]([C:2]2[CH:11]=[CH:10][C:9]3[N:8]=[CH:7][C:6]4[N:12]([CH3:22])[C:13](=[O:21])[N:14]([CH:15]5[CH2:20][CH2:19][O:18][CH2:17][CH2:16]5)[C:5]=4[C:4]=3[CH:3]=2)=[CH:26][CH:25]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 1185234078-bromo-3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one

Product 1

HCID 1185020408-(6-Fluoropyridin-3-yl)-3-methyl-1-(oxan-4-yl)imidazo[5,4-c]quinolin-2-oneYield 96%

Reagents, catalysts & solvents 4

HCID 24949188Di-t-butyl(3-sulfonatopropyl)phosphineCatalystHCID 178478579HCID 178478579, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Monopalladium(IV) disodium tetrachloride (0.975 g, 3.31 mmol) was added to 8-bromo-3-methyl-1-(oxan-4-yl)imidazo[5,4-c]quinolin-2-one (60.0 g, 165.64 mmol), (6-fluoropyridin-3-yl)boronic acid (25.7 g, 182.21 mmol), K2CO3 (68.7 g, 496.93 mmol) and 3-(di-tert-butylphosphino)propane-1-sulfonic acid (0.445 g, 1.66 mmol) in 1,4-dioxane (400 mL) and water (100 mL) at r.t. under air. The resulting mixture was stirred at 80° C. for 16 h. The reaction mixture was dilated with water and the precipitate collected by filtration, washed with water (200 mL) and dried under vacuum. The resulting solid was dissolved with DCM (18 L) and the mixture filtered through celite to remove Palladium residues. The solvent was removed under reduced pressure to afford the desired material (60.0 g, 96%) as a white solid, which was used without further purification, NMR Spectrum: 1H NMR (400 MHz, CDCl3) δ 1.85-2.01 (2H, m), 2.86-3.02 (2H, m), 3.57-3.68 (5H, m), 4.16-4.31 (2H, m), 5.11 (1H, t), 6.98-7.19 (1H, m), 7.83 (1H, dd), 8.16 (1H, td), 8.30 (1H, dd), 8.50 (1H, s), 8.60 (1H, s), 8.77 (1H, s). Mass Spectrum: m/z (ES+)[M+H]+=379.2.

Workup

  1. filtrationthe precipitate collected by filtration
  2. washwashed with water (200 mL)
  3. customdried under vacuum
  4. dissolutionThe resulting solid was dissolved with DCM (18 L)
  5. filtrationthe mixture filtered through celite
  6. customto remove Palladium residues
  7. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-8b95965457b64b9f929458dbee93c14a
Source dataset
uspto-grants-2016_08
Patent number
US09428503B2

Reaction notes

Loading…