Ethylene Glycol → 5-(3,5-Dimethylisoxazol-4-yl)-3-(2-hydroxyethoxy)-3-phenylindolin-2-one

HRID 1052958Notes

Reaction equation

HRID 1052958 reaction equation
Cl[C:2]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[C:12]([CH3:17])=[N:13][O:14][C:15]=3[CH3:16])[CH:9]=2)[NH:4][C:3]1=[O:18].N1C=CC=CC=1.[CH2:31]([OH:34])[CH2:32][OH:33]>C1COCC1.O>[CH3:17][C:12]1[C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][C:3](=[O:18])[C:2]3([O:33][CH2:32][CH2:31][OH:34])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:15]([CH3:16])[O:14][N:13]=1

Participants

6

Reactant 3

HCID 174Ethylene GlycolHCID 1049PyridineHCID 862828633-Chloro-5-(3,5-dimethylisoxazol-4-yl)-3-phenylindolin-2-one

Product 1

HCID 862828625-(3,5-Dimethylisoxazol-4-yl)-3-(2-hydroxyethoxy)-3-phenylindolin-2-oneYield 15.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

30 mg (0.088 mmol) of 3-chloro-5-(3,5-dimethylisoxazol-4-yl)-3-phenylindolin-2-one and 139 mg (0.176 mmol) of pyridine were dissolved in 5 ml of THF. After the addition of 54 mg (0.88 mmol) of ethane-1,2-diol, the reaction solution was stirred for 5 h at room temperature. Subsequently, the solution was diluted with water. The aqueous phase was extracted with 2×25 mL of EtOAc. The combined organic phases were washed with aqueous NaHCO3 and with water, dried and concentrated in vacuo. The resulting residue was purified by Pre-TLC (eluent: Hexane/EtOAc=1/1) to give product (5 mg, 15%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.77 (s, 1H), 7.32-7.35 (m, 6H), 7.20 (s, 1H), 7.04 (d, J=8.0 Hz, 1H), 4.65 (t, J=5.6 Hz, 1H), 3.23-3.52 (m, 4H), 2.35 (s, 3H), 2.18 (s, 3H). MS (ESI) m/e [M+1]+ 365.

Workup

  1. extractionThe aqueous phase was extracted with 2×25 mL of EtOAc
  2. washThe combined organic phases were washed with aqueous NaHCO3 and with water
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by Pre-TLC (eluent: Hexane/EtOAc=1/1)

Sources & evidence

ORD record
ord-6022c8ba81044770a59d2055b5e010f7
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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