Methyl iodide → HCID 57781146, compound

HRID 1690765Notes

Reaction equation

HRID 1690765 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]([CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[NH:12][C:11]2([CH3:22])[CH3:21])[CH:7]=[N:8][CH:9]=1)=[O:4].[H-].[Na+].[CH3:25]I>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[N:12]([CH3:25])[C:11]2([CH3:22])[CH3:21])[CH:7]=[N:8][CH:9]=1)=[O:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57781144HCID 57781144, compound

Product 1

HCID 57781146HCID 57781146, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 3-(3,3-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinolin-4-yl)-3H-imidazole-4-carboxylic acid methyl ester (55 mg, 0.184 mmol) in DMF (3.7 mL) at −10° C. is added sodium hydride (60% dispersion in oil 10 mg, 0.25 mmol). The reaction is stirred for 5 min at −10° C. and then placed at room temperature for 10 min. The resulting red solution is re-cooled to −10° C. and methyl iodide (0.025 mL, 0.40 mmol) is added dropwise. The reaction is placed at room temperature. After 10 min the yellow reaction mixture is quenched by the addition of saturated aqueous NH4Cl (ca. 1 mL). The resulting mixture is diluted with ethyl acetate and saturated aqueous NaHCO3. The layers are separated and the aqueous layer is extracted twice with ethyl acetate (ca. 10 mL). The organic layers are combined, dried with Na2SO4, filtered and concentrated in vacuo to afford 3-(2,3,3-trimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinolin-4-yl)-3H-imidazole-4-carboxylic acid methyl ester as a yellow foam requiring no further purification prior to the next transformation; HRMS (ES) m/z 300.1354 [(M+H)+; calculated for C16H18N3O3: 340.1348]; 1H NMR (400 MHz, MeOD) δ ppm 1.30 (s, 3H), 1.41 (s, 3 H), 3.10 (s, 3 H), 4.04 (br. s., 3 H), 6.85 (br. s., 1 H), 7.50 (br. s., 1 H), 7.61-7.73 (m, 2 H), 8.09-8.27 (m, 3 H).

Workup

  1. waitplaced at room temperature for 10 min
  2. temperatureThe resulting red solution is re-cooled to −10° C.
  3. customis placed at room temperature
  4. customAfter 10 min the yellow reaction mixture is quenched by the addition of saturated aqueous NH4Cl (ca. 1 mL)
  5. additionThe resulting mixture is diluted with ethyl acetate and saturated aqueous NaHCO3
  6. customThe layers are separated
  7. extractionthe aqueous layer is extracted twice with ethyl acetate (ca. 10 mL)
  8. dry with materialdried with Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-609851bee92f4319852aeb7cbb1dab4a
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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