Diisopropylethylamine → N-[3-(Quinolin-7-yloxy)propyl]-2,3-dihydro-7-methoxy-1,4-benzodioxin-2-methanamine

HRID 2254304Notes

Reaction equation

HRID 2254304 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][CH:9]([CH2:12][NH2:13])[O:8][C:7]=2[CH:14]=1.Br[CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:29]=[C:28]2[C:23]([CH:24]=[CH:25][CH:26]=[N:27]2)=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[N:27]1[C:28]2[C:23](=[CH:22][CH:21]=[C:20]([O:19][CH2:18][CH2:17][CH2:16][NH:13][CH2:12][CH:9]3[O:8][C:7]4[CH:14]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=4[O:11][CH2:10]3)[CH:29]=2)[CH:24]=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 18923874(7-Methoxy-2,3-dihydro-1,4-benzodioxin-2-YL)methanamineHCID 197450147-(3-Bromopropoxy)quinoline

Product 1

HCID 10110309N-[3-(Quinolin-7-yloxy)propyl]-2,3-dihydro-7-methoxy-1,4-benzodioxin-2-methanamineYield 28.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

2,3-Dihydro-7-methoxy-1,4-benzodioxin-2-methanamine (2.7 g, 14 mmole), 7-(3-bromopropoxy)quinoline (3.86 g, 14 mmole), and diisopropylethylamine (6.5 g, 50 mmole) were combined in 100 ml of DMF and heated at 80° C. for 24 hours under a nitrogen atmosphere. The solvent was then removed in vacuum and replaced with 500 ml of dichloromethane. The mixture was washed with 250 ml each of saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and concentrated in vacuum. The residue was column chromatographed on 200 g of silica gel using 4% methanolchloroform as eluant. The product-containing fractions were combined and concentrated in vacuum and the residue recrystallized from 50 ml of ethanol with the addition of 8 ml of 4N isopropanolic HCl to give 1.5 g of the title compound as a yellow solid dihydrochloride monohydrate, m.p. 135°-142° C.

Workup

  1. customThe solvent was then removed in vacuum
  2. washThe mixture was washed with 250 ml each of saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customchromatographed on 200 g of silica gel using 4% methanolchloroform as eluant
  7. concentrationconcentrated in vacuum
  8. customthe residue recrystallized from 50 ml of ethanol with the addition of 8 ml of 4N isopropanolic HCl

Sources & evidence

ORD record
ord-7c29aeda047b4dbfaa7fff4ccc26da3b
Source dataset
uspto-grants-1993_08
Patent number
US05235055

Reaction notes

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