Methyl iodide → HCID 58243391, compound

HRID 2361693Notes

Reaction equation

HRID 2361693 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([N:14]3[CH2:17][CH:16]([O:18][C:19]4[CH:20]=[C:21]5[C:25](=[CH:26][CH:27]=4)[NH:24][CH:23]=[CH:22]5)[CH2:15]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:30]I>CN(C=O)C.ClCCl>[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([N:14]3[CH2:15][CH:16]([O:18][C:19]4[CH:20]=[C:21]5[C:25](=[CH:26][CH:27]=4)[N:24]([CH3:30])[CH:23]=[CH:22]5)[CH2:17]3)=[O:13])[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67057879HCID 67057879, compound

Product 1

HCID 58243391HCID 58243391, compoundYield 74.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-({1-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidin-3-yl}oxy)-1H-indole (30 mg, 81 μmol) in DMF (2 ml) was added NaH (4 mg of a 60% dispersion in mineral oil, 97 μmol) at room temperature in one portion. The suspension was stirred for 30 min at room temperature under a nitrogen atmosphere then cooled to 0° C. and MeI (6 μl, 97 μmol) was added. The reaction was allowed to warm to room temperature and stirred for 16 hours then diluted with dichloromethane (30 ml) and washed twice with saturated NaHCO3 (15 ml), dried (MgSO4), filtered and concentrated at reduced pressure. The residue was purified by FCC (DCM/MeOH/NH3 with gradient, 98:2:1 to 90:10:1) to provide the title compound (23 mg, 74%) as light brown oil.

Workup

  1. temperaturethen cooled to 0° C.
  2. temperatureto warm to room temperature
  3. stirringstirred for 16 hours
  4. washwashed twice with saturated NaHCO3 (15 ml)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customThe residue was purified by FCC (DCM/MeOH/NH3 with gradient, 98:2:1 to 90:10:1)

Sources & evidence

ORD record
ord-b4c930bb5a7549769a90c427f42111d1
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

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