Water → 1-(3-(4-(2-(4,5-Dichloro-2-hydroxyphenylamino)acetyl)piperazin-1-yl)azetidin-1-yl)prop-2-en-1-one

HRID 588796Notes

Reaction equation

HRID 588796 reaction equation
Cl.[Cl:2][C:3]1[C:8]([Cl:9])=[CH:7][C:6]([NH:10][CH2:11][C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH:20]3[CH2:23][NH:22][CH2:21]3)[CH2:16][CH2:15]2)=[O:13])=[C:5]([OH:24])[CH:4]=1.CCN(CC)CC.[C:32](Cl)(=[O:35])[CH:33]=[CH2:34].O>C(Cl)Cl.CN(C=O)C>[Cl:2][C:3]1[C:8]([Cl:9])=[CH:7][C:6]([NH:10][CH2:11][C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH:20]3[CH2:23][N:22]([C:32](=[O:35])[CH:33]=[CH2:34])[CH2:21]3)[CH2:16][CH2:15]2)=[O:13])=[C:5]([OH:24])[CH:4]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 13140Acryloyl chlorideHCID 1317344462-(4,5-Dichloro-2-hydroxyphenylamino)-1-(4-(azetidin-3-yl)piperazin-1-yl)ethanone hydrochloride

Product 1

HCID 783191201-(3-(4-(2-(4,5-Dichloro-2-hydroxyphenylamino)acetyl)piperazin-1-yl)azetidin-1-yl)prop-2-en-1-oneYield 24.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

2-(4,5-dichloro-2-hydroxyphenylamino)-1-(4-(azetidin-3-yl)piperazin-1-yl)ethanone hydrochloride (120 mg, 0.30 mmol) was added to the mixture of Et3N (0.2 mL, 1.44 mmol) in DCM (10 mL) followed by addition of DMF (1 drop). The mixture was stirred for 5 min and then acryloyl chloride (27 mg, 0.30 mmol) was added. The resulting mixture was stirred at room temperature for 1 h, poured into water and then extracted with MeOH/DCM. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography on silica gel (DCM/MeOH/NH3.H2O=50:1:0.1 to 20:1:0.2) to afford the desired product (30 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6) δ: 10.17 (s, 1H), 6.78 (s, 1H), 6.71 (s, 1H), 6.30 (dd, J=10.4, 17.2 Hz, 1H), 6.09 (dd, J=2.0, 17.2 Hz, 1H), 5.67 (dd, J=2.4, 10.4 Hz, 1H), 5.32 (t, J=4.4 Hz, 1H), 4.26-4.22 (m, 1H), 4.11-4.04 (m, 1H), 3.93-3.91 (m, 3H), 3.79-3.75 (m, 3H), 3.52-3.51 (m, 4H), 3.19-3.16 (m, 1H), 2.36-2.30 (m, 4H). ESI-MS m/z: 411.2 [M−H]−.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 1 h
  2. extractionextracted with MeOH/DCM
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on silica gel (DCM/MeOH/NH3.H2O=50:1:0.1 to 20:1:0.2)

Sources & evidence

ORD record
ord-9cea1befb2244767be6c04ac9b7b07b8
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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