Water → HCID 69658574, compound

HRID 2212978Notes

Reaction equation

HRID 2212978 reaction equation
C([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]#[N:13])[CH:10]=2)[N:5]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:4]=1)=O.[C:24]1([CH:29]2CNCC2)[CH2:28][CH2:27][CH2:26][CH:25]=1.[OH2:34]>C1C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[O:34]=[C:25]1[CH2:26][CH2:27][CH2:28][C:24]1=[CH:29][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]#[N:13])[CH:10]=2)[N:5]([S:14]([C:17]2[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=2)(=[O:15])=[O:16])[CH:4]=1

Participants

6

Reactant 3

HCID 962WaterHCID 111747273-formyl-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrileHCID 21955951HCID 21955951, compound

Product 1

HCID 69658574HCID 69658574, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 241BenzeneSolvent

Procedure

A solution of 3-formyl-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrile (6.0 g, 18.5 mMol) and 4-(1−cyclopentenyl)pyrrolidine (3.05 g, 22.2 mMol) in benzene (200 mL) containing p-toluenesufonic acid (100 mg) were heated to reflux with azeotropic removal of water for 2 h. The solution was cooled and concentrated to dryness. The residue was then dissolved in THF (100 mL) and methanol (50 mL) and 6 N HCl (100 mL) was added dropwise with stirring over 15 min. The solution was stirred for 48 h and concentrated in vacuo. The residue was dissolved in chloroform/methanol (9:1), extracted with brine (3×250 mL), and dried over Na2SO4. The solution was concentrated and the residue was purified by silica gel column chromatography (20% ethyl acetate/hexanes-90% ethyl acetate/hexanes) to give 3-(2-oxo-cyclopent-ylidenemethyl)-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrile (3.0 g, 42%). 1H NMR (400 MHz, CDCl3) δ 8.07 (2H, d, J=6.4 Hz), 7.85 (1H, s), 7.80 (2H, d, J=6.8 Hz), 7.61 (1H, dd, J=8.8 Hz, 1.2 Hz), 7.46 (1H, t, J=2.8 Hz), 7.29 (2H, d, J=8.0 Hz), 2.91 (2H, m), 2.47 (2H, m), 2.37 (3H, s), 2.12 (2H, m); MS m/e 391 (M+H)+.

Workup

  1. temperaturewere heated
  2. temperatureThe solution was cooled
  3. concentrationconcentrated to dryness
  4. dissolutionThe residue was then dissolved in THF (100 mL)
  5. additionmethanol (50 mL) and 6 N HCl (100 mL) was added dropwise
  6. stirringThe solution was stirred for 48 h
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in chloroform/methanol (9:1)
  9. extractionextracted with brine (3×250 mL)
  10. dry with materialdried over Na2SO4
  11. concentrationThe solution was concentrated
  12. customthe residue was purified by silica gel column chromatography (20% ethyl acetate/hexanes-90% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-bf80cc552562472793a46d7b34fec209
Source dataset
uspto-grants-2006_09
Patent number
US07105516B2

Reaction notes

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