Methyl iodide → HCID 69718845, compound

HRID 896351Notes

Reaction equation

HRID 896351 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:41])[NH:9][CH2:10][C:11]1[CH:40]=[CH:39][C:14]2[N:15]([CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[C:16]([CH2:18][N:19]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:22](=[O:29])[N:21]([CH:30]4[CH2:32][CH2:31]4)[C:20]3=[O:33])=[N:17][C:13]=2[CH:12]=1)([CH3:6])([CH3:5])[CH3:4].I[CH3:43]>CN(C=O)C>[C:3]([O:7][C:8](=[O:41])[N:9]([CH2:10][C:11]1[CH:40]=[CH:39][C:14]2[N:15]([CH2:34][CH2:35][CH:36]([CH3:37])[CH3:38])[C:16]([CH2:18][N:19]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:22](=[O:29])[N:21]([CH:30]4[CH2:32][CH2:31]4)[C:20]3=[O:33])=[N:17][C:13]=2[CH:12]=1)[CH3:43])([CH3:5])([CH3:4])[CH3:6]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69718855[2-(3-cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-1-(3-methyl-butyl)-1H-benzoimidazol-5-ylmethyl]-carbamic acid tert-butyl ester

Product 1

HCID 69718845HCID 69718845, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (60% mineral oil, 11.2 mg, 0.28 mmol) in DMF (2 mL) at room temperature was added [2-(3-cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-1-(3-methyl-butyl)-1H-benzoimidazol-5-ylmethyl]-carbamic acid tert-butyl ester (50 mg, 0.094 mmol). After stirring for 5 min iodomethane (47 μL, 0.75 mmol) was added. The mixture was stirred overnight under a nitrogen atmosphere and partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate and the combined organic phases washed with 5% sodium meta-bisulfite and brine. After drying over MgSO4 the residue was purified by flash chromatography (eluent 2% MeOH in CH2Cl2) to give [2-(3-cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-1-(3-methyl-butyl)-1H-benzoimidazol-5-ylmethyl]-methyl-carbamic acid tert-butyl ester (39 mg, 76%) as a white solid:

Workup

  1. additionwas added
  2. custompartitioned between water and ethyl acetate
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. washthe combined organic phases washed with 5% sodium meta-bisulfite and brine
  5. dry with materialAfter drying over MgSO4 the residue
  6. customwas purified by flash chromatography (eluent 2% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-2bafe5858fb54777bf156ed851ce8cb0
Source dataset
uspto-grants-2005_07
Patent number
US06919331B2

Reaction notes

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