2-(Methylamino)ethanol → 4-(2-(2,3-Dihydrobenzofuran-5-yl)-1-(6-(2-(methylamino)-ethoxy)pyridin-3-yl)but-1-enyl)phenol

HRID 626258Notes

Reaction equation

HRID 626258 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][OH:5].[H-].[Na+].Cl[C:9]1[N:14]=[CH:13][C:12]([C:15]([C:28]2[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=2)=[C:16]([C:19]2[CH:20]=[CH:21][C:22]3[O:26][CH2:25][CH2:24][C:23]=3[CH:27]=2)[CH2:17][CH3:18])=[CH:11][CH:10]=1>C1COCC1>[O:26]1[C:22]2[CH:21]=[CH:20][C:19]([C:16]([CH2:17][CH3:18])=[C:15]([C:28]3[CH:29]=[CH:30][C:31]([OH:34])=[CH:32][CH:33]=3)[C:12]3[CH:13]=[N:14][C:9]([O:5][CH2:4][CH2:3][NH:2][CH3:1])=[CH:10][CH:11]=3)=[CH:27][C:23]=2[CH2:24][CH2:25]1

Participants

5

Reactant 3

HCID 80162-(Methylamino)ethanolHCID 24758Sodium hydrideHCID 1235660194-(1-(6-Chloropyridin-3-yl)-2-(2,3-dihydrobenzofuran-5-yl)but-1-enyl)phenol

Product 1

HCID 781350084-(2-(2,3-Dihydrobenzofuran-5-yl)-1-(6-(2-(methylamino)-ethoxy)pyridin-3-yl)but-1-enyl)phenolYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-(methylamino)ethanol (875 mg, 10 eq) in 20 mL anhydrous THF was added NaH (373 mg, 8.0 eq) at 0° C., and the mixture was stirred at rt for 1 h, 4-(1-(6-Chloropyridin-3-yl)-2-(2,3-dihydrobenzofuran-5-yl)but-1-enyl)phenol (440 mg, 1.0 eq) was added. The mixture was refluxed for 16 h, cooled, quenched with sat. NH4Cl, and extracted with CH2Cl2. The extract was dried, concentrated, and purified by column chromatography to give the desired product (197 mg, 41%). 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J=2.4 Hz, 0.5H), 7.60 (d, J=2.0 Hz, 0.5H), 7.32 (dd, J=8.4 Hz, 2.4 Hz, 0.5H), 7.07 (dd, J=8.4 Hz, 2.4 Hz, 0.5H), 7.03 (d, J=8.8 Hz, 1H), 6.93 (d, J=8.4 Hz, 1H), 6.83 (d, J=8.4 Hz, 0.5H), 6.78 (d, J=8.4 Hz, 1.5H), 6.69 (d, J=8.4 Hz, 1H), 6.65 (d, J=8.4 Hz, 0.5H), 6.59 (d, J=8.0 Hz, 1H), 6.49 (d, J=8.8 Hz, 1H), 6.36 (d, J=8.4 Hz, 0.5H), 4.53 (t, J=8.4 Hz, 2H), 4.46 (t, J=5.2 Hz, 1H), 4.31 (t, J=5.2 Hz, 1H), 3.10 (t, J=8.4 Hz, 2H), 3.05 (t, J=5.2 Hz, 1H), 2.96 (t, J=5.2 Hz, 1H), 2.55 (s, 1.5H), 2.50 (s, 1.5H), 2.45 (q, J=7.6 Hz, 2H), 0.94 (t, J=7.2 Hz, 3H); m/z=417[M+1]+.

Workup

  1. temperatureThe mixture was refluxed for 16 h
  2. temperaturecooled
  3. customquenched with sat. NH4Cl
  4. extractionextracted with CH2Cl2
  5. customThe extract was dried
  6. concentrationconcentrated
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-90244decd7194a11b0f4048083364680
Source dataset
uspto-grants-2016_04
Patent number
US09309211B2

Reaction notes

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