Methyl iodide → HCID 86663517, compound

HRID 2406561Notes

Reaction equation

HRID 2406561 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([CH:8]=[C:9]([C:24]#[N:25])[C:10]([NH:12][CH:13]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[CH2:14][CH2:15][CH3:16])=[O:11])[CH:5]=[CH:4][CH:3]=1.CI.[C:28](=O)([O-])[O-].[K+].[K+].[C:34]([O:37][CH2:38][CH3:39])(=O)C>CC(C)=O>[Br:1][C:2]1[N:7]=[C:6](/[CH:8]=[C:9](\[C:24]#[N:25])/[C:10]([NH:12][CH:13]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:28])=[CH:19][CH:18]=2)[CH2:14][CH2:15][CH3:16])=[O:11])[CH:5]=[CH:4][CH:3]=1.[Br:1][C:2]1[N:7]=[C:6](/[CH:8]=[C:9](/[C:24]#[N:25])\[C:10]([NH:12][CH:13]([C:17]2[CH:22]=[CH:39][C:38]([O:37][CH3:34])=[CH:19][CH:18]=2)[CH2:14][CH2:15][CH3:16])=[O:11])[CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 86663519HCID 86663519, compound

Product 2

HCID 86663517HCID 86663517, compoundYield 42%HCID 86663518HCID 86663518, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 3-(6-bromopyridin-2-yl)-2-cyano-N-(1-(4-hydroxyphenyl)butyl)acrylamide (21 mg, 0.05 mmol) in acetone was added MeI (32.6 μL, 0.52 mmol) and potassium carbonate powder (7.25 mg, 0.05 mmol). The resulting mixture was stirred at room temperature for 4 hours before the addition of ethyl acetate. The organic solution was then washed with water (1×), saturated brine (1×), dried over sodium sulfate and concentrated to give a yellow oil as the crude product. The crude material was purified with preparative TLC plate to afford (E)-3-(6-bromopyridin-2-yl)-2-cyano-N-(1-(4-methoxyphenyl)butyl)acrylamide (8) as a light yellow solid (9.2 mg, 42% yield) and (Z)-3-(6-bromopyridin-2-yl)-2-cyano-N-(1-(4-methoxyphenyl)butyl)acrylamide (9) as a white solid (4.4 mg, 20% yield). Mass spec ES+, m/z=414.0 (m+H+). E-isomer (8): 1H NMR (500 MHz, CDCl3/CD3OD) δ 7.59 (t, J=7.7, 1H), 7.52 (d, J=8.0, 1H), 7.27 (d, J=8.7, 2H), 7.22 (d, J=7.4, 1H), 6.83 (d, J=8.9, 2H), 6.81 (s, 1H), 3.89-3.83 (m, 2H), 3.81 (s, 3H), 1.65 (dd, J=15.4, 7.9, 2H), 1.39 (dd, J=15.1, 7.5, 2H), 0.94 (t, J=7.4, 3H). Z-isomer (9): 1H NMR (500 MHz, CDCl3) δ 7.83 (s, 1H), 7.79 (d, J=7.6, 1H), 7.61 (t, J=7.8, 1H), 7.52 (d, J=7.9, 1H), 7.15 (d, J=8.8, 2H), 6.93 (d, J=8.8, 2H), 3.84 (s, 3H), 3.84-3.79 (m, 2H), 1.57 (dd, J=14.8, 7.1, 5H), 1.37 (dq, J=15.0, 7.5, 2H), 0.94 (t, J=7.4, 3H).

Workup

  1. washThe organic solution was then washed with water (1×), saturated brine (1×)
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customto give a yellow oil as the crude product
  5. customThe crude material was purified with preparative TLC plate

Sources & evidence

ORD record
ord-85e672277e66408db7b9d39000973c44
Source dataset
uspto-grants-2014_08
Patent number
US08809377B2

Reaction notes

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