5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → HCID 12114958, compound

HRID 433138Notes

Reaction equation

HRID 433138 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:22][CH2:21][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[CH2:22][CH2:21][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 12114957[(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate

Product 1

HCID 12114958HCID 12114958, compoundYield 69.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of [(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate (0.348 g, 1.00 mmol) in methyl sulfoxide (20 mL) was added 5-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (0.865 g, 4.00 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, ethyl acetate:hexanes 4:1) followed by recrystallization from ethanol provided 0.271 g (69%, 40% ee) of 5-fluoro-3-(1-{[(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl}-1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole as a tan crystalline powder. [α]D25=−22.05 (c 9.98 in chloroform, 40% ee); Rf=0.49 (silica, ethyl acetate:hexanes 4:1); mp 177-180° C. dec; Anal. Calcd. for C24H25FN2O2: C, 73.45; H, 6.42; N, 7.14. Found: C, 73.03; H, 6.49; N, 7.12.

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, ethyl acetate:hexanes 4:1)
  7. customfollowed by recrystallization from ethanol

Sources & evidence

ORD record
ord-9ed62d66694b4b62bca841120e358c07
Source dataset
uspto-grants-2003_12
Patent number
US06667322B2

Reaction notes

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