Triethylamine → N-(2-(1-(2-((4,5-Dichloro-2-hydroxyphenyl)amino)acetyl)piperidin-4-yl)ethyl)acrylamide

HRID 588813Notes

Reaction equation

HRID 588813 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([NH:9][CH2:10][C:11]([OH:13])=O)=[C:4]([OH:14])[CH:3]=1.[NH:15]1[CH2:20][CH2:19][CH:18]([CH2:21][CH2:22][NH:23][C:24](=[O:27])[CH:25]=[CH2:26])[CH2:17][CH2:16]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(CC)CC>CN(C=O)C>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([NH:9][CH2:10][C:11]([N:15]2[CH2:20][CH2:19][CH:18]([CH2:21][CH2:22][NH:23][C:24](=[O:27])[CH:25]=[CH2:26])[CH2:17][CH2:16]2)=[O:13])=[C:4]([OH:14])[CH:3]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1176105992-(4,5-Dichloro-2-hydroxyphenylamino)acetic acidHCID 117610809N-(2-(Piperidin-4-yl)ethyl)acrylamide

Product 1

HCID 90463620N-(2-(1-(2-((4,5-Dichloro-2-hydroxyphenyl)amino)acetyl)piperidin-4-yl)ethyl)acrylamideYield 35.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-((4,5-dichloro-2-hydroxyphenyl)amino)acetic acid (200 mg, 0.85 mmol) in DMF (30 mL) at room temperature, N-(2-(piperidin-4-yl)ethyl)acrylamide (222.8 mg, 1.02 mmol) was added followed by HOBt (172.9 mg, 1.28 mmol), EDCI.HCl (244.7 mg, 1.28 mmol) and Et3N (257.9 mg, 2.55 mmol). The reaction mixture was stirred at room temperature for 1 h and then partitioned between ethyl acetate and brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (1-3% methanol/dichloroethane) to afford the desired product (120 mg, 29% yield) as a solid. 1H NMR (400 MHz, DMSO-d6) δ: 10.15 (s, 1H), 8.07 (t, J=5.2 Hz, 1H), 6.78 (s, 1H), 6.72 (s, 1H), 6.18 (dd, J=10.0, 17.2 Hz, 1H), 6.06 (dd, J=2.4, 17.2 Hz, 1H), 5.56 (dd, J=2.4, 10.4 Hz, 1H), 5.34 (t, J=4.0 Hz, 1H), 4.36 (d, J=12.8 Hz, 1H), 3.94-3.87 (m, 3H), 3.20-3.15 (m, 2H), 2.98-2.92 (m, 1H), 2.63-2.57 (m, 1H), 1.74-1.69 (m, 2H), 1.57-1.52 (m, 1H), 1.41-1.35 (m, 2H), 1.12-0.95 (m, 2H). ESI-MS m/z: 400.4[M+H]+.

Workup

  1. custompartitioned between ethyl acetate and brine
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography on silica gel (1-3% methanol/dichloroethane)

Sources & evidence

ORD record
ord-20ed75b4d48a48dea137e092c8c8ffc1
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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