5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → HCID 10223484, compound

HRID 585051Notes

Reaction equation

HRID 585051 reaction equation
[N:1]1[C:14]2[C:5](=[C:6]3[C:11](=[CH:12][CH:13]=2)[CH2:10][CH2:9][CH:8]([CH2:15]OS(C2C=CC(C)=CC=2)(=O)=O)[O:7]3)[CH:4]=[CH:3][CH:2]=1.[F:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][CH:32]=[C:31]2[C:37]1[CH2:38][CH2:39][NH:40][CH2:41][CH:42]=1>CS(C)=O>[F:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][CH:32]=[C:31]2[C:37]1[CH2:38][CH2:39][N:40]([CH2:15][CH:8]2[CH2:9][CH2:10][C:11]3[C:6](=[C:5]4[C:14](=[CH:13][CH:12]=3)[N:1]=[CH:2][CH:3]=[CH:4]4)[O:7]2)[CH2:41][CH:42]=1

Participants

4

Reactant 2

HCID 113449595-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 22734543HCID 22734543, compound

Product 1

HCID 10223484HCID 10223484, compoundYield 6.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
77.5 °C

Procedure

Toluene-4-sulfonic acid 7,8-dihydro-6H-5-oxa-1-aza-phenanthren-6-ylmethyl ester (0.22 g, 1.67 mmole) and 5-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (4.0 g, 1.8 mmole) were combined in 200 mL of DMSO and heated at 75-80° C. under nitrogen for 13 hours. After cooling to room temperature, the mixture was partitioned between 400 mL each of ethyl acetate and saturated sodium bicarbonate solution. The organic phase was removed, washed with saturated brine, dried over magnesium sulfate and concentrated to an oil in vacuum. This was column chromatographed on silica gel using first methylene chloride to elute impurities and then 5% methanol in methylene chloride to elute the product, 0.19 g of a yellow oil. The oil was recrystallized from isopropanol with the addition of 0.05 g of oxalic acid to give 0.043 g of the title compound as a yellow solid (m.p. 148° C.).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between 400 mL each of ethyl acetate and saturated sodium bicarbonate solution
  3. customThe organic phase was removed
  4. washwashed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated to an oil in vacuum
  7. customThis was column chromatographed on silica gel using first methylene chloride
  8. washto elute impurities
  9. wash5% methanol in methylene chloride to elute the product, 0.19 g of a yellow oil
  10. customThe oil was recrystallized from isopropanol with the addition of 0.05 g of oxalic acid

Sources & evidence

ORD record
ord-c333e795915c43f3ae119fcc5da05972
Source dataset
uspto-grants-2005_08
Patent number
US06930109B2

Reaction notes

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