Benzamide → N-(1-(2-(7-Methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridin-3-yl)benzamide

HRID 1878716Notes

Reaction equation

HRID 1878716 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[CH:13][CH:12]=2)[CH:7]=1.[C:24]([NH2:32])(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Cu]I>[CH3:22][O:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([O:10][CH2:9][CH2:8][N:6]3[C:5](=[O:23])[CH:4]=[CH:3][C:2]([NH:32][C:24](=[O:31])[C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:7]3)=[CH:12][CH:13]=[N:14]2)=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 2331BenzamideHCID 10796Cesium carbonateHCID 248844955-Bromo-1-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-one

Product 1

HCID 25019423N-(1-(2-(7-Methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridin-3-yl)benzamide

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 5-bromo-1-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1 H)-one (220 mg, 586 μmol), benzamide (213 mg, 1759 μmol), n,n′-dimethylethylenediamine (189 μl, 1759 μmol), copper(I) iodide (167 mg, 879 μmol), and cesium carbonate (573 mg, 1759 μmol) in toluene (3 mL) was sparged with argon then heated to 120° C. for 90 min. The mixture was partioned between CH2Cl2 and 5% NaHCO3 and the hazy organic was washed with 30% NH4OH, dried over MgSO4, and concentrated onto silica (10 g) and purified on silica (12 g) eluting with 0 to 6% of 2M NH3 in MeOH/CH2Cl2. A solid crystallized upon evaporation of selected fractions as a white solid. MS (ESI pos. ion) m/z (MH+): 416. Calc'd exact mass for C24H21N3O4: 415. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.07 (s, 1 H) 8.62 (d, J=4.5 Hz, 1 H) 8.19 (d, J=9.0 Hz, 1 H) 7.96 (d, J=7.5 Hz, 2 H) 7.51-7.66 (m, 4 H) 7.28 (d, J=2.5 Hz, 1 H) 7.03 (dd, J=9.0, 2.5 Hz, 1 H) 6.92 (d, J=5.5 Hz, 1 H) 6.48 (d, J=10.0 Hz, 1 H), 4.48 (s, 4 H), 3.86 (s, 3 H).

Workup

  1. customwas sparged with argon
  2. washthe hazy organic was washed with 30% NH4OH
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated onto silica (10 g)
  5. custompurified on silica (12 g)
  6. washeluting with 0 to 6% of 2M NH3 in MeOH/CH2Cl2
  7. customA solid crystallized upon evaporation of selected fractions as a white solid

Sources & evidence

ORD record
ord-1dfde620e8f64702a5cf6bee2f991fa0
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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