Iodoethane → HCID 66906316, compound

HRID 1690768Notes

Reaction equation

HRID 1690768 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+].[CH2:25](I)[CH3:26]>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]([CH2:25][CH3:26])[C:11]2([CH3:22])[CH3:21])[CH:7]=[N:8][CH:9]=1)=[O:4]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 57781144HCID 57781144, compound

Product 1

HCID 66906316HCID 66906316, 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 (114 mg, 0.381 mmol) (Example 33c) in DMF (6 mL) at −10° C. is added NaH [60% dispersion in oil (20 mg, 0.5 mmol)]. The reaction is stirred at −10° C. for 10 min, placed at room temperature for 5 min, and then recooled to −10° C., at which time ethyl iodide (0.070 mL, 0.875 mmol) is added. After 45 min the reaction is quenched with saturated aqueous NH4Cl, diluted with ethyl acetate and saturated aqueous NaHCO3. The layers are separated and the aqueous layer is extracted two more 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 (ethyl acetate-dichloromethane, 1:7 to 1:0) to afford 3-(2-ethyl-3,3-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinolin-4-yl)-3H-imidazole-4-carboxylic acid methyl ester; HRMS: (ESI) m/z 328.1673 [(M+H)+: Calcd for C18H22N3O3: 328.1661]; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J=7.1 Hz, 3 H), 1.24 (s, 3 H), 1.40 (s, 3 H), 3.47-3.57 (m, 1 H), 3.67-3.78 (m, 1H), 3.94 (s, 3 H), 6.56 (s, 1 H), 7.28-7.33 (m, 1 H), 7.42 (s, 1 H), 7.46-7.55 (m, 2 H), 7.77 (s, 1 H), 8.20-8.26 (m, 1 H).

Workup

  1. waitplaced at room temperature for 5 min
  2. additionis added
  3. customAfter 45 min the reaction is quenched with saturated aqueous NH4Cl
  4. additiondiluted with ethyl acetate and saturated aqueous NaHCO3
  5. customThe layers are separated
  6. extractionthe aqueous layer is extracted two more times with ethyl acetate
  7. dry with materialThe combined organic layers are dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 1:7 to 1:0)

Sources & evidence

ORD record
ord-04a1f2a6e2a74d218b87385ec0677fc6
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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