Indole → 1-[7-(Indole-1-sulfonyl)-3,4-dihydro-1H-isoquinolin-2-yl]-ethanone

HRID 22816

Reaction equation

HRID 22816 reaction equation
[OH-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1.[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:30]([N:33]1[CH2:42][CH2:41][C:40]2[C:35](=[CH:36][C:37]([S:43](Cl)(=[O:45])=[O:44])=[CH:38][CH:39]=2)[CH2:34]1)(=[O:32])[CH3:31]>O1CCCC1>[N:3]1([S:43]([C:37]2[CH:36]=[C:35]3[C:40]([CH2:41][CH2:42][N:33]([C:30](=[O:32])[CH3:31])[CH2:34]3)=[CH:39][CH:38]=2)(=[O:44])=[O:45])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1

Participants

6

Reactant 4

HCID 798IndoleHCID 14798Sodium HydroxideHCID 2723671Tetrabutylammonium HydroxideHCID 126069042-Acetyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonyl chloride

Product 1

HCID 225920211-[7-(Indole-1-sulfonyl)-3,4-dihydro-1H-isoquinolin-2-yl]-ethanoneYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 50% solution of sodium hydroxide (100 ml) was added to a vigorously stirred solution of indole (5.8 g, 50 mmol) and tetrabutylammonium hydroxide (40% by weight solution, 2 ml, 3.1 mmol) in tetrahydrofuran (100 ml). After 5 minutes, a solution of 2-acetyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonyl chloride (R. G. Pendleton et al., J. Pharmacol. Exp. Ther., 1979, 208, 24; U.S. Pat. No. 3,725,388 (1973)) (13.7 g, 50 mmol) in tetrahydrofuran (50 ml) was added over 10 minutes and the resulting mixture was vigorously stirred for a further 3 h. The mixture was then extracted with ethyl acetate (250 ml) and the extract dried (MgSO4), concentrated in vacuo and the residue purified by column chromatography over silica gel eluting with a dichloromethane/methanol gradient to give the title compound (D1) (12.8 g, 72%), NMR (CDCl3; rotamers observed)/ppm 2.12, 2.14 (3H, 2×s), 2.77-2.88 (2H, m), 3.60, 3.74 (3H, 2×t J=7 Hz), 4.59, 4.68 (2H, 2×s), 6.65-6.67 (1H, m), 7.16-7.34 (3H, m), 7.50-7.69 (4H, m), 7.94-7.99 (1H, m); MS: m/z (MH+) 355.

Workup

  1. extractionThe mixture was then extracted with ethyl acetate (250 ml)
  2. dry with materialthe extract dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customthe residue purified by column chromatography over silica gel eluting with a dichloromethane/methanol gradient

Sources & evidence

ORD record
ord-14f05329adb54f16b989eb56a01c6cfa
Source dataset
uspto-grants-2005_02
Patent number
US06849644B2

Linked notes

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