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 1368357Notes

Reaction equation

HRID 1368357 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-82d6c6e257e64efc868920c60df80471
Source dataset
uspto-grants-2003_06
Patent number
US06573283B2

Reaction notes

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