5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → HCID 69998437, compound

HRID 433142Notes

Reaction equation

HRID 433142 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[CH:22]=[CH:21][C:20]3[C:15](=[C:16]([O:23][CH3:24])[CH:17]=[CH:18][CH:19]=3)[O:14]2)(=O)=O)=CC=1.[F:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][CH:30]=[C:29]2[C:35]1[CH2:36][CH2:37][NH:38][CH2:39][CH:40]=1>CS(C)=O.C(OCC)(=O)C>[F:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][CH:30]=[C:29]2[C:35]1[CH2:36][CH2:37][N:38]([CH2:12][C@H:13]2[CH:22]=[CH:21][C:20]3[C:15](=[C:16]([O:23][CH3:24])[CH:17]=[CH:18][CH:19]=3)[O:14]2)[CH2:39][CH:40]=1

Participants

5

Reactant 2

HCID 113449595-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 12114962HCID 12114962, compound

Product 1

HCID 69998437HCID 69998437, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of [(2R)-8-methoxy-2H-chromen-2-yl]methyl 4-methyl-benzenesulfonate (0.350 g, 1.01 mmol) in methyl sulfoxide (20 mL) was added 5-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (0.655 g, 3.03 mmol) and the reaction mixture was heated to 80° C. for 12 h. The reaction mixture was allowed to cool to room temperature and was diluted with ethyl acetate (200 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 0.240 g (61%, >97% ee) of 5-fluoro-3-(1-{[(2R)-8-methoxy-2H-chromen-2-yl]methyl}-1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole as a yellow solid. [α]D25=−2.14 (c 10.27 in chloroform, >97% ee); Rf=0.49 (silica, methanol:ethyl acetate 1:9); mp 189-191° C. dec; Anal. Calcd. for C24H23FN2O2.0.3 H2O: C, 73.15; H, 5.99; N, 7.11. Found: C, 73.19; H, 6.03; N, 7.08.

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-721ffe9957e64f9981fb5a4f124bcbc7
Source dataset
uspto-grants-2003_12
Patent number
US06667322B2

Reaction notes

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