Ethyl Acetate → HCID 131727469, compound

HRID 883614Notes

Reaction equation

HRID 883614 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH2:13][NH:12][CH2:11]3)[CH:8]=[CH:9][C:2]1=2.Cl.[CH3:21][N:22]([CH3:26])[CH2:23][CH2:24]Cl.[C:27](=[O:30])([O-:29])[O-].[Cs+].[Cs+].[C:33]([O:36]CC)(=[O:35])C>CN(C=O)C>[C:33]([OH:36])(=[O:35])/[CH:23]=[CH:24]/[C:27]([OH:29])=[O:30].[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH2:13][N:12]([CH2:24][CH2:23][N:22]([CH3:26])[CH3:21])[CH2:11]3)[CH:8]=[CH:9][C:2]1=2

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 11536296HCID 11536296, compoundHCID 11636816N,N-Dimethylaminoethyl chloride hydrochloride

Product 1

HCID 131727469HCID 131727469, compoundYield 2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-benzo[b]thiophen-5-yl-1,2,3,4-tetrahydroisoquinoline (250 mg, 0.94 mmol, the preparation of which was described in Example 20), 2-dimethylaminoethylchloride, hydrochloride salt (271 mg, 1.89 mmol), and cesium carbonate (1.23 g, 3.77 mmol) in DMF (4 mL) was stirred at room temperature for 3 days. The mixture was diluted with ethyl acetate, washed with 5% LiOH solution, then brine, and the organic layer dried over magnesium sulfate, and concentrated. The residue was purified by column chromatography (SiO2, 12 g, 85% to 0% hexane/ethyl acetate) to provide the desired tetrahydroisoquinoline (7.0 mg, 2%). This material was dissolved in methanol and treated with a solution of fumaric acid in methanol (5 mL) at 0° C. The solution was stirred at room temperature for 12 hours, then concentrated, and the solid was washed with diethyl ether providing [2-(4-benzo[b]thiophen-5-yl-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]dimethylamine, fumarate salt (9.2 mg, 98%, 97.2% AUC HPLC): 1H NMR (CD3OD, 500 MHz) δ 7.82 (d, J=8.3 Hz, 1H), 7.63 (d, J=1.4 Hz, 1H), 7.54 (d, J=5.5 Hz, 1H), 7.29-7.28 (m, 1H), 7.20-7.10 (m, 4H), 6.90-6.88 (m, 1H), 6.75 (s, 2H), 4.46-4.44 (m, 1H), 4.04-3.94 (m, 2H), 3.16-2.98 (m, 6H), 2.64 (s, 3H), 2.60 (s, 3H); ESI-MS m/z=337 [M+H]+.

Workup

  1. customthe preparation of which
  2. washwashed with 5% LiOH solution
  3. dry with materialbrine, and the organic layer dried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (SiO2, 12 g, 85% to 0% hexane/ethyl acetate)

Sources & evidence

ORD record
ord-2f42cfea960f4584b8e3c8f71b76a9de
Source dataset
uspto-grants-2012_08
Patent number
US08236796B2

Reaction notes

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