5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → HCID 10140200, compound

HRID 1167375Notes

Reaction equation

HRID 1167375 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:30][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[C:21]([CH2:26][CH3:27])[C:20]([CH2:28][CH3:29])=[N:19]4)(=O)=O)=CC=1.[F:31][C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[NH:37][CH:36]=[C:35]2[C:41]1[CH2:42][CH2:43][NH:44][CH2:45][CH:46]=1>CS(C)=O.C(OCC)(=O)C>[CH2:26]([C:21]1[C:20]([CH2:28][CH3:29])=[N:19][C:18]2[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14][CH:13]([CH2:12][N:44]4[CH2:43][CH:42]=[C:41]([C:35]5[C:34]6[C:38](=[CH:39][CH:40]=[C:32]([F:31])[CH:33]=6)[NH:37][CH:36]=5)[CH2:46][CH2:45]4)[O:30][C:17]3=2)[N:22]=1)[CH3:27]

Participants

5

Reactant 2

HCID 113449595-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 12082523HCID 12082523, compound

Product 1

HCID 10140200HCID 10140200, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (2R)-8,9-diethyl-2,3-dihydro[1,4]dioxino[2,3-f]-quinoxalin-2-ylmethyl 4-methylbenzenesulfonate (0.300 g, 0.700 mmole) in methyl sulfoxide (20 mL) was added 5-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1 H-indole (0.606 g, 2.800 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 0.161 g (49%) of the (S)-enantiomer of the title compound as a yellow crystalline solid. Rf =0.38 (silica, methanol:ethyl acetate 1:9); mp>120° C. dec.

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-c492ae8b639c415a8a145de931f8647a
Source dataset
uspto-grants-2003_09
Patent number
US06617327B2

Reaction notes

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