3-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indole → HCID 10273302, compound

HRID 1359062Notes

Reaction equation

HRID 1359062 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:27][C:17]3=[C:18]4[C:23](=[C:24]([F:26])[CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[CH:21][CH:20]=[CH:19]4)(=O)=O)=CC=1.[NH:28]1[CH2:33][CH:32]=[C:31]([C:34]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[NH:36][CH:35]=2)[CH2:30][CH2:29]1>CS(C)=O>[F:26][C:24]1[CH:25]=[C:16]2[O:15][CH2:14][CH:13]([CH2:12][N:28]3[CH2:29][CH:30]=[C:31]([C:34]4[C:42]5[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=5)[NH:36][CH:35]=4)[CH2:32][CH2:33]3)[O:27][C:17]2=[C:18]2[C:23]=1[N:22]=[CH:21][CH:20]=[CH:19]2

Participants

4

Reactant 2

HCID 27610233-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indoleHCID 86586351HCID 86586351, compound

Product 1

HCID 10273302HCID 10273302, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
77.5 °C

Procedure

0.40 g (1.02 mmole) of (2R)-6-fluoro-2,3-dihydro[1,4]dioxino[2,3-f]-quinolin-2-ylmethyl 4-methylbenzenesulfonate and 0.80 g (4.06 mmole) of 3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole were combined in 50 mL of DMSO. The mixture was heated at 75-80° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL each of ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was removed, washed with saturated brine, dried over magnesium sulfate, filtered and concentrated to a crude oil under vacuum. This oil was column chromatographed on silica gel using first 1% methanol in methylene chloride to elute impurities and then 5% methanol in methylene chloride to elute the product. The product-containing fractions were concentrated in vacuum to give 0.085 g of the (S)-enantiomer of the title compound as a yellow solid (m.p. 215° C.).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between 400 mL each of ethyl acetate and saturated aqueous sodium bicarbonate
  3. customThe organic phase was removed
  4. washwashed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to a crude oil under vacuum
  8. customchromatographed on silica gel using first 1% methanol in methylene chloride
  9. washto elute impurities
  10. wash5% methanol in methylene chloride to elute the product
  11. concentrationThe product-containing fractions were concentrated in vacuum

Sources & evidence

ORD record
ord-3934d93cf45343548b368d17a13da009
Source dataset
uspto-grants-2003_07
Patent number
US06599915B2

Reaction notes

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