1-(2-Hydroxyethyl)piperazine → HCID 178431371, compound

HRID 333399Notes

Reaction equation

HRID 333399 reaction equation
F[C:2]1[CH:28]=[CH:27][C:5]([C:6]([NH:8][C:9]2[C:10]([CH3:26])([CH3:25])[O:11]/[C:12](=[C:14]3/[C:15](=[O:24])[NH:16][C:17]4[C:22]/3=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=4)/[CH:13]=2)=[O:7])=[CH:4][N:3]=1.[OH:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>CN(C=O)C.C(OCC)(=O)C>[F:23][C:19]1[CH:18]=[C:17]2[C:22](/[C:14](=[C:12]3/[CH:13]=[C:9]([NH:8][C:6](=[O:7])[C:5]4[CH:27]=[CH:28][C:2]([N:35]5[CH2:36][CH2:37][N:32]([CH2:31][CH2:30][OH:29])[CH2:33][CH2:34]5)=[N:3][CH:4]=4)[C:10]([CH3:26])([CH3:25])[O:11]/3)/[C:15](=[O:24])[NH:16]2)=[CH:21][CH:20]=1

Participants

5

Reactant 2

HCID 76771-(2-Hydroxyethyl)piperazineHCID 178431369HCID 178431369, compound

Product 1

HCID 178431371HCID 178431371, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
66 °C

Procedure

To a stirred solution of 6-fluoro-N-[(5E)-5-(6-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]nicotinamide (75 mg, 0.20 mmol) in DMF (3 mL) was added 1-(2-hydroxyethyl)piperazine (70 mg, 0.54 mmol). The reaction mixture was heated in 66° C. bath for 30 minutes, cooled to room temperature, and diluted with ethyl acetate (80 mL). The ethyl acetate solution was washed with brine (4×20 mL), dried over Na2SO4, and concentrated to give the crude product. Purification of the crude product by silica gel chromatography with a gradient of methanol in chloroform (5-20%) gave N-[(5E)-5-(6-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]-6-[4-(2-hydroxyethyl)piperazin-1-yl]nicotinamide as a yellow solid. Yield: 42 mg, 43%.

Workup

  1. temperaturecooled to room temperature
  2. washThe ethyl acetate solution was washed with brine (4×20 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customto give the crude product
  6. customPurification of the crude product by silica gel chromatography with a gradient of methanol in chloroform (5-20%)

Sources & evidence

ORD record
ord-ba656aa3db764f03adf3e1e110de7570
Source dataset
uspto-grants-2014_11
Patent number
US08877923B2

Reaction notes

Loading…