Methyl iodide → (6-{Methyl-[5-(3-trifluoromethoxy-phenyl)-pent-4-ynoyl]-amino}-indol-1-yl)-acetic acid

HRID 751206Notes

Reaction equation

HRID 751206 reaction equation
C([O:3][C:4](=[O:33])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([NH:15][C:16](=[O:32])[CH2:17][CH2:18][C:19]#[C:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([O:27][C:28]([F:31])([F:30])[F:29])[CH:22]=3)[CH:13]=2)[CH:8]=[CH:7]1)C.[H-].[Na+].CI.[C:38](OCC)(=O)C>O1CCCC1>[CH3:38][N:15]([C:16](=[O:32])[CH2:17][CH2:18][C:19]#[C:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][C:28]([F:30])([F:29])[F:31])[CH:22]=1)[C:12]1[CH:13]=[C:14]2[C:9]([CH:8]=[CH:7][N:6]2[CH2:5][C:4]([OH:3])=[O:33])=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 8857Ethyl AcetateHCID 24758Sodium hydride2×HCID 69275123{6-[5-(3-Trifluoromethoxy-phenyl)-pent-4-ynoylamino]-indol-1-yl}-acetic acid ethyl ester

Product 1

HCID 11612000(6-{Methyl-[5-(3-trifluoromethoxy-phenyl)-pent-4-ynoyl]-amino}-indol-1-yl)-acetic acidYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

{6-[5-(3-Trifluoromethoxy-phenyl)-pent-4-ynoylamino]-indol-1-yl}-acetic acid ethyl ester (50 mg, 0.11 mmol) was added to a suspension of sodium hydride (9 mg, 0.22 mmol) in tetrahydrofuran (1.5 ml) at 0° C. The mixture was stirred for 30 min at 0° C., methyl iodide (30 μl, 0.44 mmol) was added and stirring was continued for 14 h at ambient temperature. The suspension was cooled to 0° C., sodium hydride (13 mg, 0.33 mmol) and methyl iodide (45 μl, 0.66 mmol) were added and the mixture was stirred for 4 h at ambient temperature. Ethyl acetate was added, the solution was successively washed with brine, 1 N HCl/ice water 1/1 and brine and dried over sodium sulfate. The solvent was removed under reduced pressure to give 42 mg (0.09 mmol, 82%) of the title compound as yellow solid.

Workup

  1. stirringstirring
  2. waitwas continued for 14 h at ambient temperature
  3. temperatureThe suspension was cooled to 0° C.
  4. stirringthe mixture was stirred for 4 h at ambient temperature
  5. washthe solution was successively washed with brine, 1 N HCl/ice water 1/1 and brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-564514fd8bbd411b97136ebd33fb8585
Source dataset
uspto-grants-2008_07
Patent number
US07405236B2

Reaction notes

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