Dimethyl Sulfoxide → HCID 22139470, compound

HRID 1825717Notes

Reaction equation

HRID 1825717 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][CH:4]([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:16]#[N:17])[CH:14]=3)[NH:9][CH:8]=2)[CH2:3]1.[H-].[Na+].[CH3:20]S(C)=O>CI>[CH3:20][N:9]1[C:10]2[C:15](=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=2)[C:7]([CH:4]2[CH2:5][CH2:6][C:2](=[O:1])[CH2:3]2)=[CH:8]1

Participants

5

Reactant 3

HCID 679Dimethyl Sulfoxide2×HCID 24758Sodium hydrideHCID 22139459HCID 22139459, compound

Product 1

HCID 22139470HCID 22139470, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6328Methyl iodideCatalyst

Conditions

Temperature
40 °C

Procedure

3-(3-oxocyclopentyl)-1H-indole-5-carbonitrile (11.21 g, 0.05 mMol) was dissolved in anhydrous DMSO (30 mL) and added dropwise to a suspension of sodium hydride (2.25 g, 0.055 mMol, 60% in mineral oil) in dry DMSO (50 mL) under nitrogen at 25–30° C. The reaction was heated to 40° C. for 15 min, then cooled to room temperature. Methyl iodide (3.42 mL, 0.055 mMol) was added dropwise, maintaining reaction temperature at 25–30° C. with an external ice water bath. After stirring for 2 h at room temperature, the reaction was poured into 1 L ice water. The tan solid was filtered, washed with H2O, dissolved in ethyl acetate (750 mL), extracted with H2O (500 mL) and brine (500 mL), and dried over sodium sulfate. The ethyl acetate extract was concentrated in vacuo and the product was purified by chromatography on silica gel with a 10% step gradient of 25–45% ethyl acetate in hexane. Pure product fractions were concentrated in vacuo and dried under high vacuum to give 1-methyl-3-(3-oxo-cyclopentyl)-1H-indole-5-carbonitrile (8.52 g, 72%). 1H NMR (500 MHz, CDCl3) δ 7.95 (1 H, s), 7.46 (1 H, dd, J=8.54, 1.22), 7.34 (1 H, d, J=8.54), 6.94 (1 H, s), 3.78 (3 H, s), 3.69 (1 H, m), 2.74 (1 H, dd, J=7.63, 18.01 Hz), 2.53 (1 H, m), 2.38 (3 H, m), 2.06 (1 H, m). MS m/e 239.3 (M+H)+. Anal. calcd. for C15H14N2O: C, 75.60; H, 5.92; N, 11.75. Found: C, 75.31; H, 5.86; N, 11.55. IR (KBr) 2219, 1728 cm−1.

Workup

  1. temperaturecooled to room temperature
  2. temperaturemaintaining
  3. customreaction temperature at 25–30° C. with an external ice water bath
  4. filtrationThe tan solid was filtered
  5. washwashed with H2O
  6. dissolutiondissolved in ethyl acetate (750 mL)
  7. extractionextracted with H2O (500 mL) and brine (500 mL)
  8. dry with materialdried over sodium sulfate
  9. extractionThe ethyl acetate extract
  10. concentrationwas concentrated in vacuo
  11. customthe product was purified by chromatography on silica gel with a 10% step gradient of 25–45% ethyl acetate in hexane
  12. concentrationPure product fractions were concentrated in vacuo
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-e565d69d18ad4108bb4eb76475520f14
Source dataset
uspto-grants-2006_05
Patent number
US07049314B2

Reaction notes

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