Trifluoroacetic acid → 5-(3,5-Dimethylisoxazol-4-yl)-3-phenyl-3-(piperazin-1-yl)indolin-2-one

HRID 1052964Notes

Reaction equation

HRID 1052964 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([N:23]2[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:5]([CH3:36])[O:4][N:3]=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl.O>[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:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[C:5]([CH3:36])[O:4][N:3]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 117668248Tert-butyl 4-(5-(3,5-dimethylisoxazol-4-yl)-2-oxo-3-phenylindolin-3-yl)piperazine-1-carboxylate

Product 1

HCID 862813775-(3,5-Dimethylisoxazol-4-yl)-3-phenyl-3-(piperazin-1-yl)indolin-2-oneYield 71.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-(5-(3,5-dimethylisoxazol-4-yl)-2-oxo-3-phenylindolin-3-yl)piperazine-1-carboxylate (0.9 g, 1.8 mmol) in CH2Cl2 (5 mL) was added TFA (5 mL) at 0° C., after adding up, the reaction was stirred at room temperature for 2.0 h. The solvent was evaporated in vacuo to give crude product. It was dissolved in water (20 mL), and was neutralized with NaHCO3 to PH=7˜8, and then the mixture was extracted with EtOAc (2×30 mL), combined organic phase, dried with Na2SO4, filtrated, concentrated to give crude product, and the mixture was purified by chromatography (eluent. CH2Cl2/MeOH/NH3H2O=20/1/0.05) to give product (500 mg, 71.6%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δH 10.75 (s, 1H), 7.49 (d, J=8.0 Hz, 2H), 7.23-7.36 (m, 5H), 6.97 (d, J=8.0 Hz, 1H), 2.65-2.66 (m, 4H), 2.31-2.47 (m, 7H), 2.19 (s, 3H). MS (ESI) m/e [M+1]+ 389.

Workup

  1. additionafter adding up
  2. customThe solvent was evaporated in vacuo
  3. customto give crude product
  4. extractionthe mixture was extracted with EtOAc (2×30 mL)
  5. dry with materialdried with Na2SO4
  6. filtrationfiltrated
  7. concentrationconcentrated
  8. customto give crude product
  9. customthe mixture was purified by chromatography (eluent. CH2Cl2/MeOH/NH3H2O=20/1/0.05)

Sources & evidence

ORD record
ord-2c9692cf409d4039a5cda26b75f5d945
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

Loading…