Methyl iodide → HCID 58505629, compound

HRID 1917610Notes

Reaction equation

HRID 1917610 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[N:19]3[C:14]([CH:15]=[C:16]([CH:20]([CH3:22])[CH3:21])[CH:17]=[CH:18]3)=[C:13]([C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])[C:12]=2[CH2:29][C:30]([CH3:37])([CH3:36])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[O:10])=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:41]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([CH3:41])[C:9]([C:11]2[N:19]3[C:14]([CH:15]=[C:16]([CH:20]([CH3:21])[CH3:22])[CH:17]=[CH:18]3)=[C:13]([C:23](=[O:28])[C:24]([CH3:25])([CH3:26])[CH3:27])[C:12]=2[CH2:29][C:30]([CH3:37])([CH3:36])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[O:10])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58505583HCID 58505583, compound

Product 1

HCID 58505629HCID 58505629, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of ethyl 3-{3-[(4-bromophenyl)carbamoyl]-1-(2,2-dimethylpropanoyl)-7-(propan-2-yl)indolizin-2-yl}-2,2-dimethylpropanoate (100 mg, 0.18 mmol) in DMF (2 mL) is added NaH (60% dispersion in mineral oil, 7.7 mg, 0.19 mmol) at 0° C. The suspension is stirred for 10 minutes then iodomethane (12.0 μl 0.19 mmol) is introduced and the reaction mixture is stirred overnight. The mixture is quenched with water, extracted with EtOAc, dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by flash chromatography (SiO2, hexanes to 40% EtOAc in hexanes) gives ethyl 3-{3-[(4-bromophenyl)(methyl)carbamoyl]-1-(2,2-dimethylpropanoyl)-7-(propan-2-yl)indolizin-2-yl}-2,2-dimethylpropanoate (75 mg, 73%) that is dissolved in THF (8 mL), MeOH (1 mL), and water (1 mL) and treated with 10M aqueous NaOH (0.1 mL). The mixture is stirred for 16 h then concentrated and acidified with HOAc. The resulting solid is filtered, washed with water, collected, and dried to give the title compound (50 mg, 70%).

Workup

  1. stirringthe reaction mixture is stirred overnight
  2. customThe mixture is quenched with water
  3. extractionextracted with EtOAc
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the crude by flash chromatography (SiO2, hexanes to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c08fb4d880db45cf8be2321109683697
Source dataset
uspto-grants-2013_12
Patent number
US08618300B2

Reaction notes

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