Methyl iodide → 4-imidazol-1-yl-2,3,3-trimethyl-3,4-dihydro-2H-isoquinolin-1-one

HRID 1690773Notes

Reaction equation

HRID 1690773 reaction equation
[N:1]1([CH:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[NH:8][C:7]2([CH3:18])[CH3:17])[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].[CH3:21]I>CN(C=O)C>[N:1]1([CH:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[N:8]([CH3:21])[C:7]2([CH3:18])[CH3:17])[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 577811054-Imidazol-1-yl-3,3-dimethyl-2,4-dihydroisoquinolin-1-one

Product 1

HCID 577811164-imidazol-1-yl-2,3,3-trimethyl-3,4-dihydro-2H-isoquinolin-1-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-imidazol-1-yl-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-one, which can be prepared as described in Example 36d (140 mg, 0.58 mmol) in DMF (8 mL) at −10° C. is added NaH [60% dispersion in oil (30 mg, 0.75 mmol)]. After 10 min, the reaction is warmed to room temperature for 5 min and then re-cooled to −10° C. The reaction is then charged with methyl iodide (0.075 mL, 1.2 mmol) and placed at room temperature. After 20 min, the reaction is cooled to −10° C., quenched with saturated aqueous NH4Cl, and diluted with saturated aqueous NaHCO3 and ethyl acetate. The layers are separated and the aqueous layer is extracted two times with ethyl acetate. The combined organic layers are dried over Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (methanol-dichloromethane, 0:1 to 1:12) to afford 4-imidazol-1-yl-2,3,3-trimethyl-3,4-dihydro-2H-isoquinolin-1-one; HRMS (ESI) m/z 256.1448 [(M+H)+: Calcd for C15H18N3O: 256.1450]; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.22 (s, 3 H), 1.33 (s, 3 H), 3.09 (s, 3 H), 5.01 (s, 1 H), 6.78 (s, 1 H), 7.02 (s, 1 H), 7.20 (d, J=3.8 Hz, 1 H), 7.47-7.57 (m, 3 H), 8.20-8.28 (m, 1 H).

Workup

  1. temperaturere-cooled to −10° C
  2. customplaced at room temperature
  3. waitAfter 20 min
  4. temperaturethe reaction is cooled to −10° C.
  5. customquenched with saturated aqueous NH4Cl
  6. additiondiluted with saturated aqueous NaHCO3 and ethyl acetate
  7. customThe layers are separated
  8. extractionthe aqueous layer is extracted two times with ethyl acetate
  9. dry with materialThe combined organic layers are dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe resulting residue is purified by silica gel flash chromatography (methanol-dichloromethane, 0:1 to 1:12)

Sources & evidence

ORD record
ord-86c6f8db2dad4dbaa9c89edf2b93fa67
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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