Triethylamine → N-(1-(1-(2-(4,5-Dichloro-2-hydroxyphenylamino)acetyl)azetidin-3-yl)azetidin-3-yl)acrylamide

HRID 588799Notes

Reaction equation

HRID 588799 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.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC.Cl.[NH:45]1[CH2:48][CH:47]([N:49]2[CH2:52][CH:51]([NH:53][C:54](=[O:57])[CH:55]=[CH2:56])[CH2:50]2)[CH2:46]1>CN(C=O)C.O>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([NH:9][CH2:10][C:11]([N:45]2[CH2:46][CH:47]([N:49]3[CH2:52][CH:51]([NH:53][C:54](=[O:57])[CH:55]=[CH2:56])[CH2:50]3)[CH2:48]2)=[O:13])=[C:4]([OH:14])[CH:3]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 90460006N-(1-(Azetidin-3-yl)azetidin-3-yl)acrylamide hydrochlorideHCID 1176105992-(4,5-Dichloro-2-hydroxyphenylamino)acetic acid

Product 1

HCID 86279627N-(1-(1-(2-(4,5-Dichloro-2-hydroxyphenylamino)acetyl)azetidin-3-yl)azetidin-3-yl)acrylamideYield 3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(4,5-dichloro-2-hydroxyphenylamino)acetic acid (120 mg, 0.51 mmol), EDCI.HCl (147 mg, 0.77 mmol), HOBt (83 mg, 0.61 mmol), Et3N (154 mg, 1.53 mmol) in DMF (20 mL) was stirred at room temperature for 5 min and then N-(1-(azetidin-3-yl)azetidin-3-yl)acrylamide hydrochloride (150 mg, 0.69 mmol) was added. The resulting mixture was stirred at room temperature for 15 h. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated NaHCO3 solution and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (DCM/MeOH/NH3.H2O=100:10:1.5) to afford the desired product (6 mg, 3% yield). 1H NMR (400 MHz, DMSO-d6) δ: 10.19 (s, 1H), 8.59 (d, J=8.0 Hz, 1H), 6.79 (s, 1H), 6.55 (s, 1H), 6.20 (dd, J=10.0, 16.8 Hz, 1H), 6.09 (dd, J=2.0, 16.8 Hz, 1H), 5.62 (dd, J=2.0, 9.6 Hz, 1H), 5.20 (t, J=4.0 Hz, 1H), 4.40-4.35 (m, 1H), 4.19-4.15 (m, 1H), 3.96-3.88 (m, 2H), 3.73-3.69 (m, 3H), 3.53-3.45 (m, 3H), 3.00-2.96 (m, 2H). ESI-MS m/z: 399.2[M+H]+.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 15 h
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated NaHCO3 solution and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel (DCM/MeOH/NH3.H2O=100:10:1.5)

Sources & evidence

ORD record
ord-7c4455ae637e429ab423ff41056139f8
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

Loading…