Diisopropylcarbodiimide → [4-(5-Fluoro-1H-indole-3-yl)-butyl]-(7-methoxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-amine

HRID 1290263Notes

Reaction equation

HRID 1290263 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][CH2:13][C:14](O)=O.O.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C.Cl.[CH3:38][O: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>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][CH2:13][CH2:14][NH:50][CH2:49][CH:46]1[O:45][C:44]2[CH:51]=[C:40]([O:39][CH3:38])[CH:41]=[CH:42][C:43]=2[O:48][CH2:47]1

Participants

6

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 150472684-(5-Fluoro-1H-indol-3-yl)butanoic acidHCID 189238737-Methoxy-2,3-dihydro-1,4-benzodioxin-2-methanamine hydrochloride

Product 1

HCID 18923877[4-(5-Fluoro-1H-indole-3-yl)-butyl]-(7-methoxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-amineYield 57.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

5-Fluoroindole-3-butyric acid (1.2 g, 5.4 mmole), 1-hydroxybenzotriazole hydrate (0.88 g, 6.5 mmole) and 1,3-diisopropylcarbodiimide (2.0 ml, 13.0 mmole) were combined in 150 ml of DMF and stirred at room temperature for 2 hours under a nitrogen atmosphere. To this was added dropwise 7-methoxy-2,3-dihydro-1,4-benzodioxin-2-methanamine hydrochloride (1.3 g, 5.4 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 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 1.2 g (56%) of the desired product, (7-methoxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-4-(5-fluoro-1H-indole-3-yl)-butanamide, as an oil.

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-9dcbee9b310c40039567ee627463f23c
Source dataset
uspto-grants-1998_05
Patent number
US05750724

Reaction notes

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