3-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indole → 8-[4-(1H-Indol-3-yl)-3,6-dihydro-2H-pyridin-1-ylmethyl]-2-trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthalene

HRID 584594Notes

Reaction equation

HRID 584594 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:22][C:21]3[C:16](=[CH:17][CH:18]=[C:19]4[NH:25][C:24]([C:26]([F:29])([F:28])[F:27])=[N:23][C:20]4=3)[O:15][CH2:14]2)(=O)=O)=CC=1.[NH:30]1[CH2:35][CH:34]=[C:33]([C:36]2[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[NH:38][CH:37]=2)[CH2:32][CH2:31]1>CS(C)=O.C(OCC)(=O)C>[NH:38]1[C:39]2[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:36]([C:33]2[CH2:34][CH2:35][N:30]([CH2:12][CH:13]3[O:22][C:21]4[C:16](=[CH:17][CH:18]=[C:19]5[NH:25][C:24]([C:26]([F:27])([F:29])[F:28])=[N:23][C:20]5=4)[O:15][CH2:14]3)[CH2:31][CH:32]=2)=[CH:37]1

Participants

5

Reactant 2

HCID 27610233-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indoleHCID 12071004[(8R)-2-trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthalen-8-yl]methyl 4-methylbenzenesulfonate

Product 1

HCID 101826358-[4-(1H-Indol-3-yl)-3,6-dihydro-2H-pyridin-1-ylmethyl]-2-trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthaleneYield 73.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 0.50 g (1.2 mmole) of [(8R)-2-trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthalen-8-yl]methyl 4-methylbenzenesulfonate and 1.0 g (5.0 mmole) of 3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole in 8.0 mL of DMSO was heated at 85° C. under nitrogen for 6 hours. The reaction was allowed to come to room temperature, diluted to 400 mL with ethyl acetate, washed with 400 mL portions of saturated aqueous sodium bicarbonate, water and saturated brine, dried over sodium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on silica gel with 1% methanol in chloroform as eluant and the product fractions concentrated in vacuum to give 0.40 g of the desired compound as the free base. Recrystallization from ethanol with the addition of 0.12 g of fumaric acid gave 0.24 g of the (S)-enantiomer of the title compound as a pale yellow solid fumarate, m.p. 231-233° C.

Workup

  1. customto come to room temperature
  2. washwashed with 400 mL portions of saturated aqueous sodium bicarbonate, water and saturated brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuum
  6. customchromatographed on silica gel with 1% methanol in chloroform as eluant
  7. concentrationthe product fractions concentrated in vacuum

Sources & evidence

ORD record
ord-09ab30535a9d46c19b69cfd3aaa2e78e
Source dataset
uspto-grants-2005_08
Patent number
US06927226B2

Reaction notes

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