Morpholine → (1H-Indol-6-yl)(morpholino)methanone

HRID 2361241Notes

Reaction equation

HRID 2361241 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16](O)=[O:17])[CH:14]=2)[CH:9]=[CH:8]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C.CCOCC.O>[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[O:17])[CH:14]=2)[CH:9]=[CH:8]1

Participants

9

Reactant 5

HCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5952301H-indole-6-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 39710543(1H-Indol-6-yl)(morpholino)methanoneYield 76%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of morpholine (1.320 mL, 15.14 mmol), 1H-indole-6-carboxylic acid (2.0332 g, 12.62 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (3.63 g, 18.92 mmol), 1-hydroxybenzotriazole (HOBt) (2.90 g, 18.92 mmol) and diisopropylethylamine (DIPEA) (6.61 mL, 37.8 mmol) in DMF (31.5 mL) was stirred overnight. The reaction was poured into a 1:1 water:brine solution and extracted with EtOAc (2×). The organic layers were combined and washed with 0.25 M aqueous KHSO4, water, brine and 10% aqueous LiCl; dried over Na2SO4, filtered and concentrated in vacuo. Trituration with Et2O provided the desired product (2.20 g, 9.58 mmol, 76% yield) as a light tan solid.

Workup

  1. extractionbrine solution and extracted with EtOAc (2×)
  2. washwashed with 0.25 M aqueous KHSO4, water, brine and 10% aqueous LiCl
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bf5e8fa28c884a42946249507c720335
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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