1H-Indole-3-propanoic acid → N-(3-{[3-(1H-Indol-3-yl)-propylamino]methyl}-2,3-dihydro-benzo[1,4]dioxin-6-yl)-methanesulfonamide

HRID 1290265Notes

Reaction equation

HRID 1290265 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][C:12](O)=O)=[CH:2]1.O.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C.[CH3:35][S:36]([NH:39][C:40]1[CH:41]=[CH:42][C:43]2[O:48][CH2:47][CH:46]([CH2:49][NH2:50])[O:45][C:44]=2[CH:51]=1)(=[O:38])=[O:37]>CN(C=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][CH2:12][NH:50][CH2:49][CH:46]2[CH2:47][O:48][C:43]3[CH:42]=[CH:41][C:40]([NH:39][S:36]([CH3:35])(=[O:38])=[O:37])=[CH:51][C:44]=3[O:45]2)=[CH:2]1

Participants

6

Reactant 4

HCID 37441H-Indole-3-propanoic acidHCID 12734DiisopropylcarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 189238797-Methylsulfonylamino-2,3-dihydro-1,4-benzodioxin-2-methanamine

Product 1

HCID 18923867N-(3-{[3-(1H-Indol-3-yl)-propylamino]methyl}-2,3-dihydro-benzo[1,4]dioxin-6-yl)-methanesulfonamideYield 64.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-Indolepropionic acid (0.77 g, 4.1 mmole), 1-hydroxybenzotriazole hydrate (0.66 g, 4.9 mmole) and 1,3-diisopropylcarbodiimide (0.77 ml, 4.9 mmole) were combined in 75 ml of DMF and stirred at room temperature for 2 hours under a nitrogen atmosphere. To this was added dropwise 7-methylsulfonylamino-2,3-dihydro-1,4-benzodioxin-2-methanamine (1.0 g, 4.1 mmole) in 50 ml of DMF and the mixture was further stirred for 24 hours. The solvent was removed and the residue partitioned between dichloromethane and water. The separated dichloromethane layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The residue was chromatographed on a silica gel column using 10% hexane in ethyl acetate as the eluant. Fractions containing product were concentrated and washed with a minimum amount of THF to remove a by-product and to give 1.1 g (61%) of the desired product, (S)-(7-methylsulfonyl-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-4-(1H-indol-3-yl)-propanamide, as a white solid.

Workup

  1. stirringthe mixture was further stirred for 24 hours
  2. customThe solvent was removed
  3. customthe residue partitioned between dichloromethane and water
  4. dry with materialThe separated dichloromethane layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum
  7. customThe residue was chromatographed on a silica gel column
  8. additionFractions containing product
  9. concentrationwere concentrated
  10. washwashed with a minimum amount of THF
  11. customto remove a by-product

Sources & evidence

ORD record
ord-c1af4977d56a45a89e8fdfdb6b1f8e0d
Source dataset
uspto-grants-1998_05
Patent number
US05750724

Reaction notes

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