6-chloro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → HCID 18180310, compound

HRID 989772Notes

Reaction equation

HRID 989772 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:27][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[C:21]([CH3:26])[CH:20]=[CH:19]4)(=O)=O)=CC=1.[Cl:28][C:29]1[CH:37]=[C:36]2[C:32]([C:33]([C:38]3[CH2:39][CH2:40]NCC=3)=[CH:34][NH:35]2)=[CH:31][CH:30]=1>CS(C)=O>[Cl:28][C:29]1[CH:37]=[C:36]2[C:32]([C:33]([CH2:38][CH:39]3[CH2:40][CH2:23][N:22]([CH2:12][CH:13]4[O:27][C:17]5=[C:18]6[C:23](=[CH:24][CH:25]=[C:16]5[O:15][CH2:14]4)[N:22]=[C:21]([CH3:26])[CH:20]=[CH:19]6)[CH2:21][CH2:20]3)=[CH:34][NH:35]2)=[CH:31][CH:30]=1

Participants

4

Reactant 2

HCID 100598546-chloro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 11280604(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate

Product 1

HCID 18180310HCID 18180310, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
75 °C

Procedure

(2R)-8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.55 g, 1.4 mmole) and 6-chloro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (0.80 g, 3.4 mmole) were combined in 10 mL of DMSO. The mixture was heated at 70-80 ° 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 400 mL portions of water and saturated brine, dried over sodium sulfate, filtered and concentrated to dryness under vacuum. The residue was column chromatographed on silica gel using 0-2% methanol/chloroform. The product fractions were concentrated in vacuum to give 0.27 g of the (S)-enantiomer of the title compound as an amorphous orange solid, which retains 0.35 equivalents of chloroform.

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 400 mL portions of water and saturated brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under vacuum
  8. customchromatographed on silica gel using 0-2% methanol/chloroform
  9. concentrationThe product fractions were concentrated in vacuum

Sources & evidence

ORD record
ord-4b7dae2f06364e7fa0d46aafc1e39444
Source dataset
uspto-grants-2002_10
Patent number
US06458802B1

Reaction notes

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