4-(piperazin-1-yl)-1H-indole → 2-[4-(1H-Indol-4-yl)-piperazin-1-ylmethyl]-2,3,8,9-tetrahydro-7H-1.4-dioxino[2.3-e]indol-8-one

HRID 362249Notes

Reaction equation

HRID 362249 reaction equation
C1(C)C=CC(S(O[CH2:11][C@@H:12]2[O:25][C:16]3=[C:17]4[C:21](=[CH:22][CH:23]=[C:15]3[O:14][CH2:13]2)[NH:20][C:19](=[O:24])[CH2:18]4)(=O)=O)=CC=1.[NH:27]1[C:35]2[C:30](=[C:31]([N:36]3[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]3)[CH:32]=[CH:33][CH:34]=2)[CH:29]=[CH:28]1>CS(C)=O.C(OCC)(=O)C.CCCCCC>[NH:27]1[C:35]2[C:30](=[C:31]([N:36]3[CH2:41][CH2:40][N:39]([CH2:11][CH:12]4[O:25][C:16]5=[C:17]6[C:21](=[CH:22][CH:23]=[C:15]5[O:14][CH2:13]4)[NH:20][C:19](=[O:24])[CH2:18]6)[CH2:38][CH2:37]3)[CH:32]=[CH:33][CH:34]=2)[CH:29]=[CH:28]1

Participants

5

Reactant 2

HCID 5945904-(piperazin-1-yl)-1H-indoleHCID 15381104(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

Product 1

HCID 539317342-[4-(1H-Indol-4-yl)-piperazin-1-ylmethyl]-2,3,8,9-tetrahydro-7H-1.4-dioxino[2.3-e]indol-8-oneYield 73.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
80 °C

Procedure

(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one (1.0 g, 2.7 mmole) and 4-(1H-indol-4-yl)-piperazine (2.0 g, 10 mmole) were combined in 30 ml of dry DMSO and heated to 80° C. for 4 hours under an argon atmosphere. After cooling to room temperature, the mixture was diluted with 400 ml of 1:1 ethyl acetate/hexane and washed with 400 ml of saturated sodium bicarbonate solution, with two 250 ml portions of water and with saturated brine. The mixture was dried over sodium sulfate, filtered and concentrated in vacuum to yield an oil, which was column chromatographed on silica gel using 0.5% methanol/CHCl3 as eluant. The free base of the title compound (0.80 g) thus obtained was crystallized from methanol with the addition of one equivalent of fumaric acid to give 077 g of the (S) enantiomer of the title compound as a white solid fumarate, m.p. 237°-238° C.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with 400 ml of saturated sodium bicarbonate solution, with two 250 ml portions of water and with saturated brine
  3. dry with materialThe mixture was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customto yield an oil, which
  7. customchromatographed on silica gel using 0.5% methanol/CHCl3 as eluant

Sources & evidence

ORD record
ord-02eb8daa152b458c9fe6ffbc7c4e4ca6
Source dataset
uspto-grants-1999_02
Patent number
US05869490

Reaction notes

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