3-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indole → HCID 10158005, compound

HRID 392645Notes

Reaction equation

HRID 392645 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([OH:28])=[C:20]([NH:23][C:24]([O:26]C)=O)[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=O)=O)=CC=1.[NH:29]1[CH2:34][CH:33]=[C:32]([C:35]2[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[NH:37][CH:36]=2)[CH2:31][CH2:30]1>CS(C)=O>[NH:37]1[C:38]2[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:35]([C:32]2[CH2:33][CH2:34][N:29]([CH2:12][CH:13]3[O:18][C:17]4[C:16](=[CH:22][CH:21]=[C:20]5[NH:23][C:24](=[O:26])[O:28][C:19]5=4)[O:15][CH2:14]3)[CH2:30][CH:31]=2)=[CH:36]1

Participants

4

Reactant 2

HCID 27610233-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indoleHCID 86587694HCID 86587694, compound

Product 1

HCID 10158005HCID 10158005, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

0.85 g (2.08 mmole) of {(2R)-8-hydroxy-7-[(methoxycarbonyl)amino]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate and 1.13 g (5.70 mmole) of 3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole were combined in DMSO (40 mL) and heated at 60° C. under nitrogen for 6 hours. After completion, the reaction was cooled to room temperature and partitioned between 300 mL each of ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuum to a viscous oil. The crude oil was dissolved in methylene chloride and was heated at reflux in the presence of carbonyl diimidazole (1.02 g) for 4 hours. The reaction was allowed to cool to room temperature and the solvent was removed in vacuum. The residue was column chromatographed on silica gel using first 20% hexane/methylene chloride, then methylene chloride and finally 2% methanol/methylene chloride as eluant. The product fractions were combined and concentrated in vacuum to give 0.080 g of the (S)-enantiomer of the title compound as a light yellow solid, m.p. 202° C.

Workup

  1. temperatureAfter completion, the reaction was cooled to room temperature
  2. custompartitioned between 300 mL each of ethyl acetate and saturated aqueous sodium bicarbonate
  3. washThe organic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum to a viscous oil
  7. dissolutionThe crude oil was dissolved in methylene chloride
  8. temperaturewas heated
  9. temperatureat reflux in the presence of carbonyl diimidazole (1.02 g) for 4 hours
  10. temperatureto cool to room temperature
  11. customthe solvent was removed in vacuum
  12. customchromatographed on silica gel using first 20% hexane/methylene chloride
  13. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-0d973d26788649f696a8aa669b0b4b9b
Source dataset
uspto-grants-2004_10
Patent number
US06800648B2

Reaction notes

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