5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → HCID 10203892, compound

HRID 1743109Notes

Reaction equation

HRID 1743109 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:28][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[C:21]([CH3:26])[C:20]([CH3:27])=[N:19]4)(=O)=O)=CC=1.[F:29][C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[NH:35][CH:34]=[C:33]2[C:39]1[CH2:40][CH2:41][NH:42][CH2:43][CH:44]=1>CS(C)=O.C(OCC)(=O)C>[F:29][C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[NH:35][CH:34]=[C:33]2[C:39]1[CH2:40][CH2:41][N:42]([CH2:12][CH:13]2[O:28][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[C:21]([CH3:26])[C:20]([CH3:27])=[N:19]4)[CH2:43][CH:44]=1

Participants

5

Reactant 2

HCID 113449595-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 12082520HCID 12082520, compound

Product 1

HCID 10203892HCID 10203892, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of [(2R)-8,9-dimethyl-2,3-dihydro[1,4]dioxino[2,3-f]-quinoxalin-2-yl]methyl 4-methylbenzenesulfonate (0.400 g, 1.000 mmole) in methyl sulfoxide (20 mL) was added 5-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (0.540 g, 2.497 mmole) and the reaction mixture was heated to 80° C. for 12 hours. The reaction mixture was allowed to cool to room temperature and was diluted with ethyl acetate (250 mL), washed with water (2×100 mL), aqueous sodium chloride (100 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, methanol:ethyl acetate 1:9) followed by recrystallization from ethanol provided 0.239 g (54%) of the (S)-enantiomer of the title compound as a pale yellow solid. Rf=0.35 (silica, methanol:ethyl acetate 1:9); mp 138–141° C.

Workup

  1. temperatureto cool to room temperature
  2. washwashed with water (2×100 mL), aqueous sodium chloride (100 mL)
  3. dry with materialdried (magnesium sulfate)
  4. customthe solvent was removed in vacuo
  5. customto give a crude solid
  6. customPurification by flash column chromatography (silica, methanol:ethyl acetate 1:9)
  7. customfollowed by recrystallization from ethanol

Sources & evidence

ORD record
ord-83e5b0b4db104bee872c868051148db4
Source dataset
uspto-grants-2006_03
Patent number
US07008944B2

Reaction notes

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