5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → HCID 9887424, compound

HRID 1168708Notes

Reaction equation

HRID 1168708 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:25][C:17]3=[C:18]4[C:22](=[CH:23][CH:24]=[C:16]3[O:15][CH2:14]2)[NH:21][CH:20]=[CH:19]4)(=O)=O)=CC=1.[F:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[NH:32][CH:31]=[C:30]2[C:36]1[CH2:37][CH2:38][NH:39][CH2:40][CH:41]=1>CS(C)=O.C(OCC)(=O)C>[F:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[NH:32][CH:31]=[C:30]2[C:36]1[CH2:37][CH2:38][N:39]([CH2:12][CH:13]2[O:25][C:17]3=[C:18]4[C:22](=[CH:23][CH:24]=[C:16]3[O:15][CH2:14]2)[NH:21][CH:20]=[CH:19]4)[CH2:40][CH:41]=1

Participants

5

Reactant 2

HCID 113449595-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 12083387HCID 12083387, compound

Product 1

HCID 9887424HCID 9887424, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 0.30 g (0.84 mmole) of (2R)-2,3-dihydro-7H-[1,4]dioxino[2,3-e]indol-2-ylmethyl 4-methylbenzenesulfonate and 0.40 g (1.8 mmole) of 5-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole in 30 mL of DMSO was heated at 65° C. for 4 hours. The mixture was diluted with 300 mL of ethyl acetate, washed with 200 ml portions of saturated aqueous sodium bicarbonate and saturated brine, dried over magnesium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on silica gel with 0-1.5% methanol in methylene chloride as eluant. The product fractions were combined and concentrated in vacuum, and the residue triturated with ether/hexane (1:1) to give 0.10 g of the (S)-enantiomer of the title compound as a yellow solid, m.p. 112° C., with one-quarter mole of ether.

Workup

  1. washwashed with 200 ml portions of saturated aqueous sodium bicarbonate and saturated brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuum
  5. customchromatographed on silica gel with 0-1.5% methanol in methylene chloride as eluant
  6. concentrationconcentrated in vacuum
  7. customthe residue triturated with ether/hexane (1:1)

Sources & evidence

ORD record
ord-14b9de7a8e274eb4823acd77e721acab
Source dataset
uspto-grants-2003_09
Patent number
US06627639B2

Reaction notes

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