Sodium hydride → 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-iodo-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one

HRID 577481Notes

Reaction equation

HRID 577481 reaction equation
[I:1][C:2]1[C:3]([O:13][CH3:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.[H-].[Na+].[CH2:17]([O:24][C:25]1[C:30]([CH2:31]Cl)=[C:29]([CH3:33])[CH:28]=[C:27]([CH3:34])[N:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C=O)C>[CH2:17]([O:24][C:25]1[C:30]([CH2:31][N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[C:2]([I:1])[C:3]([O:13][CH3:14])=[CH:4][CH:5]=3)[C:10]2=[O:12])=[C:29]([CH3:33])[CH:28]=[C:27]([CH3:34])[N:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 612578682-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridineHCID 867237068-iodo-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 867237072-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-iodo-7-methoxy-3,4-dihydroisoquinolin-1(2H)-oneYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 8-iodo-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (53b, 2.08 mg, 5.22 mmol) in anhydrous DMF (30 mL) was added NaH (420 mg, 10.4 mmol, 60% in oil) at 0° C. under N2 atmosphere for 30 minutes. 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 1.89 g, 7.83 mmol) was added to the mixture. The resulting mixture was stirred at room temperature for 14 hours. The mixture was quenched with H2O (60 mL) and extracted with EtOAc (4×80 mL). The combined organic layers were washed with brine (2×50 mL), dried over Na2SO4 and concentrated under vacuum. The residue was purified by prep.HPLC to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-iodo-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (53c, 2.5 g, 91%) as a yellow solid.

Workup

  1. customThe mixture was quenched with H2O (60 mL)
  2. extractionextracted with EtOAc (4×80 mL)
  3. washThe combined organic layers were washed with brine (2×50 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by prep.HPLC

Sources & evidence

ORD record
ord-39a6e8716eb04608b920a19630b06271
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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