Potassium Acetate → 5-Methoxy-3-(1-phenyl-1H-pyrazol-5-yl)-1-quinolin-8-ylpyridazin-4(1H)-one

HRID 1407302Notes

Reaction equation

HRID 1407302 reaction equation
Br[C:2]1[C:7](=[O:8])[C:6]([O:9][CH3:10])=[CH:5][N:4]([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:20]=2[N:19]=[CH:18][CH:17]=[CH:16]3)[N:3]=1.[C:21]1([N:27]2[C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:29]=[N:28]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CC([O-])=O.[K+]>C(O)CCC.O>[CH3:10][O:9][C:6]1[C:7](=[O:8])[C:2]([C:31]2[N:27]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:28]=[CH:29][CH:30]=2)=[N:3][N:4]([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:20]=2[N:19]=[CH:18][CH:17]=[CH:16]3)[CH:5]=1

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 580723671-Phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 594361483-bromo-5-methoxy-1-quinolin-8-ylpyridazin-4(1H)-one

Product 1

HCID 580721885-Methoxy-3-(1-phenyl-1H-pyrazol-5-yl)-1-quinolin-8-ylpyridazin-4(1H)-oneYield 81.5%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 962WaterSolvent2×

Procedure

A mixture of 3-bromo-5-methoxy-1-quinolin-8-ylpyridazin-4(1H)-one (70 mg, 0.217 mmol), 1-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (88.1 mg, 0.326 mmol), KOAc (42.6 mg, 0.434 mmol) and PdCl2{P(t-Bu)2(Ph-p-NMe2)}2 (7.7 mg, 0.0109 mmol) in BuOH (1.1 mL) and water (0.1 mL) was heated to reflux for 16 h under Ar atmosphere. The mixture was diluted with water, extracted with AcOEt, washed with saturated NaHCO3 aqueous solution, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100 and AcOEt/MeOH=100/0 to 70/30) and recrystallized with AcOEt/hexane to yield the title compound (69.9 mg, 81% yield) as a white solid: mp 189-192° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.76 (3H, s), 6.98 (1H, s), 7.31-7.49 (6H, m), 7.58-7.73 (2H, m), 7.78 (1H, d, J=1.9 Hz), 8.14 (1H, d, J=8.3 Hz), 8.54 (1H, d, J=7.9 Hz), 8.67 (1H, s), 8.99 (1H, d, J=4.1 Hz). Anal. Calcd for C23H17N5O2: C, 69.86; H, 4.33; N, 17.71. Found: C, 69.61; H, 4.37; N, 17.57.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 16 h under Ar atmosphere
  3. extractionextracted with AcOEt
  4. washwashed with saturated NaHCO3 aqueous solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100 and AcOEt/MeOH=100/0 to 70/30)
  9. customrecrystallized with AcOEt/hexane

Sources & evidence

ORD record
ord-2e2359c36cb84777a27f306aa08a48b7
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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