5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → HCID 10274376, compound

HRID 1168714Notes

Reaction equation

HRID 1168714 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:27][C:17]3=[C:18]4[C:22](=[CH:23][CH:24]=[C:16]3[O:15][CH2:14]2)[NH:21][C:20]([CH2:25][CH3:26])=[CH:19]4)(=O)=O)=CC=1.[F:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][CH:33]=[C:32]2[C:38]1[CH2:39][CH2:40][NH:41][CH2:42][CH:43]=1>CS(C)=O.C(OCC)(=O)C>[CH2:25]([C:20]1[NH:21][C:22]2[C:18]([CH:19]=1)=[C:17]1[O:27][CH:13]([CH2:12][N:41]3[CH2:42][CH:43]=[C:38]([C:32]4[C:31]5[C:35](=[CH:36][CH:37]=[C:29]([F:28])[CH:30]=5)[NH:34][CH:33]=4)[CH2:39][CH2:40]3)[CH2:14][O:15][C:16]1=[CH:24][CH:23]=2)[CH3:26]

Participants

5

Reactant 2

HCID 113449595-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 12083390HCID 12083390, compound

Product 1

HCID 10274376HCID 10274376, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 0.41 g (0.1.1 mmole) of [(2R)-8-ethyl-2,3-dihydro-7H-[1,4]-dioxino[2,3-e]indol-2-yl]methyl 4-methylbenzenesulfonate and 0.71 g (3.3 mmole) of 5-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole in 25 mL of DMSO were heated at 75-80° 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 0-2% 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 0.090 g of the (S)-enantiomer of the title compound as a yellow solid hydrate, m.p. 81-82° C.

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 0-2% methanol in methylene chloride as eluant
  6. concentrationconcentrated in vacuum
  7. customthe residue triturated with ether/hexane (1:1)

Sources & evidence

ORD record
ord-ee60b9d4cebd41e2a910b9f8869b3ca9
Source dataset
uspto-grants-2003_09
Patent number
US06627639B2

Reaction notes

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