6-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → 8-[4-(6-Fluoro-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 584595Notes

Reaction equation

HRID 584595 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.[F:30][C:31]1[CH:39]=[C:38]2[C:34]([C:35]([C:40]3[CH2:41][CH2:42][NH:43][CH2:44][CH:45]=3)=[CH:36][NH:37]2)=[CH:33][CH:32]=1>CS(C)=O.C(OCC)(=O)C>[F:30][C:31]1[CH:39]=[C:38]2[C:34]([C:35]([C:40]3[CH2:41][CH2:42][N:43]([CH2:12][CH:13]4[O:22][C:21]5[C:16](=[CH:17][CH:18]=[C:19]6[NH:25][C:24]([C:26]([F:29])([F:28])[F:27])=[N:23][C:20]6=5)[O:15][CH2:14]4)[CH2:44][CH:45]=3)=[CH:36][NH:37]2)=[CH:33][CH:32]=1

Participants

5

Reactant 2

HCID 110530726-fluoro-3-(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 102990098-[4-(6-Fluoro-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

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 0.90 g (4.2 mmole) of 6-fluoro-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 and water, 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 recrystallized from ethanol with the addition of 0.10 g of fumaric acid to give 0.16 g of the (S)-enantiomer of the title compound as a yellow solid hemifumarate, hydrate, m.p. 215-220° C.

Workup

  1. customto come to room temperature
  2. washwashed with 400 mL portions of saturated aqueous sodium bicarbonate and water
  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. customrecrystallized from ethanol with the addition of 0.10 g of fumaric acid

Sources & evidence

ORD record
ord-76f543d24e5446d1958effb6726a4519
Source dataset
uspto-grants-2005_08
Patent number
US06927226B2

Reaction notes

Loading…