[2-Dimethylamino-6-methoxybenzothien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone → [2-(1-Naphthyl)-6-methoxybenzothien-3-yl][4-[2-(1-piperdinyl)ethoxy]phenyl]methanone

HRID 2191

Reaction equation

HRID 2191 reaction equation
CN(C)[C:3]1[S:4][C:5]2[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:6]=2[C:7]=1[C:8]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[CH:12][CH:11]=1)=[O:9].[C:32]1([Mg]Br)[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[CH:34][CH:33]=1>O1CCCC1>[C:40]1([C:3]2[S:4][C:5]3[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:6]=3[C:7]=2[C:8]([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[CH:14][CH:15]=2)=[O:9])[C:41]2[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:37]=[CH:38][CH:39]=1

Participants

4

Reactant 2

HCID 9954835[2-Dimethylamino-6-methoxybenzothien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanoneHCID 178418298HCID 178418298, compound

Product 1

HCID 10720792[2-(1-Naphthyl)-6-methoxybenzothien-3-yl][4-[2-(1-piperdinyl)ethoxy]phenyl]methanoneYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of [2-dimethylamino-6-methoxybenzothien-3-yl][4-[2-(1-piperdinyl)ethoxy]phenyl]methanone (1.58 g, 3.6 mmol) (see U.S. Pat. No. 5,420,349) in tetrahydrofuran (THF, 12 mL) was cooled to 0° C. and treated with a 0.65M THF solution of 1-naphthylmagnesium bromide (20.0 mL, 13 mmol) (prepared from 1-bromonaphthalene, catalytic iodine, and magnesium turnings in THF). The mixture was allowed to warm to ambient temperature and when the starting material was consumed, the reaction was quenched with water and extracted with ethyl acetate (a small amount of methanol was added to improve solubility). The organic layer was washed with water (2×), and brine (2×), dried (sodium sulfate), and concentrated. The residue was purified via chromatography (silica gel, 0-10% methanol in methylene chloride) to provide 1.08 g (58%) of the title compound as a yellow foam: 1H NMR (300 MHz, CDCl3) δ1.46 (m, 2H), 1.60 (m, 4H), 2.47 (m, 4H), 2.68 (t, J=5.9 Hz, 2H), 3.92 (s, 3H), 3.96 (t, J=5.9 Hz, 2H), 6.47 (d, J=8.8 Hz, 2H), 7.06 (dd, J=2.3 Hz, 8.9 Hz, 1H), 7.27-7.50 (m, 5H), 7.54 (d, J=8.8 Hz, 2H), 7.67-7.75 (m, 2H), 7.79 (d, J=8.9 Hz, 1H), 8.06-8.09 (m, 1H); MS (FD) m/e 521 (M+).

Workup

  1. customwhen the starting material was consumed
  2. customthe reaction was quenched with water
  3. extractionextracted with ethyl acetate (a small amount of methanol
  4. additionwas added
  5. washThe organic layer was washed with water (2×), and brine (2×)
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated
  8. customThe residue was purified via chromatography (silica gel, 0-10% methanol in methylene chloride)

Sources & evidence

ORD record
ord-a1b8d0e577394df0ad9547d14447018b
Source dataset
uspto-grants-1998_03
Patent number
US05728724

Linked notes

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