Sodium hydride → 5-Bromo-1-(2-(7-methoxyquinolin-4-yloxy)propyl)pyridin-2(1H)-one

HRID 1878699Notes

Reaction equation

HRID 1878699 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.[H-].[Na+].BrC(C)COC1C2C(=CC(OC)=CC=2)N=CC=1.Br[CH2:29][CH:30]([O:32][C:33]1[C:42]2[C:37](=[CH:38][C:39]([O:43][CH3:44])=[CH:40][CH:41]=2)[N:36]=[CH:35][CH:34]=1)[CH3:31]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[N:6]([CH2:31][CH:30]([O:32][C:33]2[C:42]3[C:37](=[CH:38][C:39]([O:43][CH3:44])=[CH:40][CH:41]=3)[N:36]=[CH:35][CH:34]=2)[CH3:29])[CH:7]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 5995285-Bromo-2-hydroxypyridineHCID 598430804-(1-Bromopropan-2-yloxy)-7-methoxyquinolineHCID 688114544-(2-Bromopropoxy)-7-methoxyquinoline

Product 1

HCID 598430605-Bromo-1-(2-(7-methoxyquinolin-4-yloxy)propyl)pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirring solution of 5-bromo-2(1H)-pyridone (100 mg, 575 μmol) in DMF (1 mL) under nitrogen was added sodium hydride (60% dispersion in mineral oil; 27.6 mg, 1149 μmol) and stirred for 10 min. To this suspension was added 4-(2-bromopropoxy)-7-methoxyquinoline (170 mg, 575 μmol) and 4-(1-bromopropan-2-yloxy)-7-methoxyquinoline (170 mg, 575 μmol) mixture in DMF (1 mL). The mixture was stirred at 40° C. for 48 h. The reaction was quenched with 5% NaHCO3 and extracted with CH2Cl2 (4×10 mL). The combined organics were dried over MgSO4, concentrated to a residue from toluene, and purified on 12 grams of silica eluting with 30-60% of 5% (MeOH/CH2Cl2). MS (ESI pos. ion) m/z (MH+): 389/391. Calc'd exact mass for C18H17BrN2O3: 388. 1H NMR (400 MHz, Chloroform-d) δ ppm 1.52 (d, J=6.26 Hz, 3H) 3.90-4.01 (m, 4H) 4.48 (dd, J=13.60, 3.23 Hz, 1H) 5.05-5.14 (m, 1H) 6.45 (d, J=9.59 Hz, 1H) 6.67 (d, J=5.48 Hz, 1H) 7.18 (dd, J=9.19, 2.54 Hz, 1H) 7.24-7.31 (m, 1H) 7.37 (d, J=2.15 Hz, 1H) 7.53 (d, J=2.54 Hz, 1H) 8.01 (d, J=9.19 Hz, 1H) 8.61 (d, J=5.48 Hz, 1H). 13C NMR (101 MHz, Chloroform-d) 8 ppm 17.29, 54.82, 55.55, 71.78, 97.82, 100.08, 107.03, 116.03, 118.81, 121.93, 122.66, 138.56, 143.08, 151.11, 151.41, 160.12, 161.17.

Workup

  1. stirringThe mixture was stirred at 40° C. for 48 h
  2. customThe reaction was quenched with 5% NaHCO3
  3. extractionextracted with CH2Cl2 (4×10 mL)
  4. dry with materialThe combined organics were dried over MgSO4
  5. concentrationconcentrated to a residue from toluene
  6. custompurified on 12 grams of silica eluting with 30-60% of 5% (MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-17796b8bae584dd0be28446627a55c78
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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