Ethyl bromoacetate → Ethyl 2-(4-(5-(3,5-dimethylisoxazol-4-yl)-2-oxo-3-phenylindolin-3-yl) piperazin-1-yl)acetate

HRID 1052965Notes

Reaction equation

HRID 1052965 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][C:11](=[O:16])[C:10]3([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[C:5]([CH3:29])[O:4][N:3]=1.Br[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33].C(=O)([O-])[O-].[K+].[K+].[NH4+].[Cl-]>CN(C=O)C>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][C:11](=[O:16])[C:10]3([N:17]2[CH2:22][CH2:21][N:20]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:19][CH2:18]2)[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[C:5]([CH3:29])[O:4][N:3]=1

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 862813775-(3,5-Dimethylisoxazol-4-yl)-3-phenyl-3-(piperazin-1-yl)indolin-2-one

Product 1

HCID 86281627Ethyl 2-(4-(5-(3,5-dimethylisoxazol-4-yl)-2-oxo-3-phenylindolin-3-yl) piperazin-1-yl)acetateYield 42.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(3,5-dimethylisoxazol-4-yl)-3-phenyl-3-(piperazin-1-yl)indolin-2-one (194 mg, 0.5 mmol) in DMF (3.0 mL) was added ethyl 2-bromoacetate (417 mg, 2.5 mmol) and potassium carbonate (208 mg, 1.5 mmol), and the mixture was stirred in RT for 0.5 h, and then saturated NH4Cl (10 mL) was added, and the mixture was extracted with CH2Cl2 (2×10 mL), combined the organic phase, dried with Na2SO4, concentrated in vacuo to give crude product. The mixture was purified with chromatography on column using CH2Cl2/MeOH (50/1, v/v) as eluting to afford a white solid (100 mg, 42%). 1H NMR (400 MHz, DMSO-d6): δH 7.52 (d, J=8.0 Hz, 2H), 7.29-7.37 (m, 5H), 7.17 (d, J=8.0 Hz, 1H), 4.65 (s, 2H), 4.16 (q, J=6.8 Hz, 2H), 2.50-2.52 (m, 4H), 2.36 (s, 3H), 218 (s, 3H), 1.17 (t, J=6.8 Hz, 3H). MS (ESI) m/e [M+1]+ 475.

Workup

  1. extractionthe mixture was extracted with CH2Cl2 (2×10 mL)
  2. dry with materialdried with Na2SO4
  3. concentrationconcentrated in vacuo
  4. customto give crude product
  5. customThe mixture was purified with chromatography on column
  6. washv/v) as eluting

Sources & evidence

ORD record
ord-4eb8ccca55314380ab87c40b0e5fd3ed
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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