Methyl iodide → HCID 25122032, compound

HRID 37881Notes

Reaction equation

HRID 37881 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:9]=[C:8]([CH3:10])[N:7]=[C:6]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:42])[C:25](=[O:41])[C:26]4[N:34]5[C:29]([CH2:30][CH2:31][CH2:32][CH2:33]5)=[CH:28][C:27]=4[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)[CH:5]=1.[CH3:43]I>C1COCC1.C(Cl)Cl>[CH3:3][C:4]1[CH:9]=[C:8]([CH3:10])[N:7]=[C:6]([N:11]2[CH2:12][CH2:13][N:14]([C:17]3[CH:18]=[CH:19][C:20]([N:23]([CH3:43])[C:24](=[O:42])[C:25](=[O:41])[C:26]4[N:34]5[C:29]([CH2:30][CH2:31][CH2:32][CH2:33]5)=[CH:28][C:27]=4[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[CH:21][CH:22]=3)[CH2:15][CH2:16]2)[CH:5]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25122029HCID 25122029, compound

Product 1

HCID 25122032HCID 25122032, compoundYield 59.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (55% dispersion in oil, 24 mg, 0.56 mmol) was added to an ice-cold solution of N-{4-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-phenyl}-2-oxo-2-(2-phenyl-5,6,7,8-tetrahydro-indolizin-3-yl)-acetamide (prepared as described in Example 3, 200 mg, 0.37 mmol) in THF, and stirred for 10 minutes at 0° C. Methyl iodide (0.036 mL, 0.56 mmol) was added, the mixture warmed to room temperature and stirred for 30 min. The solvent was evaporated and the residue partitioned between ice-water and DCM. The organic layer was separated and washed successively with water, sodium bicarbonate solution and brine, dried over sodium sulfate and concentrated to give a residue. This was dissolved in the minimum amount of DCM and re-precipitated by addition of petroleum ether to afford N-{4-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-phenyl}-N-methyl-2-oxo-2-(2-phenyl-5,6,7,8-tetrahydro-indolizin-3-yl)-acetamide (120 mg, 58%) as light yellow powder.

Workup

  1. temperaturethe mixture warmed to room temperature
  2. stirringstirred for 30 min
  3. customThe solvent was evaporated
  4. customthe residue partitioned between ice-water and DCM
  5. customThe organic layer was separated
  6. washwashed successively with water, sodium bicarbonate solution and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customto give a residue
  10. customre-precipitated by addition of petroleum ether

Sources & evidence

ORD record
ord-9a50e4dd60944484a7083b58e8a220e9
Source dataset
uspto-grants-2013_09
Patent number
US08524705B2

Reaction notes

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