Aluminium lithium hydride → 5-(3,5-Dimethylisoxazol-4-yl)-3-(4-(2-hydroxyethyl)piperazin-1-yl)-3-phenylindolin-2-one

HRID 1052966Notes

Reaction equation

HRID 1052966 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]([CH2:29][C:30](OCC)=[O:31])[CH2:25][CH2:24]2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:5]([CH3:35])[O:4][N:3]=1.[H-].[H-].[H-].[H-].[Al+3].[Li+]>C1COCC1>[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[CH2:24][CH2:25][N:26]([CH2:29][CH2:30][OH:31])[CH2:27][CH2:28]2)[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[C:5]([CH3:35])[O:4][N:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86281627Ethyl 2-(4-(5-(3,5-dimethylisoxazol-4-yl)-2-oxo-3-phenylindolin-3-yl) piperazin-1-yl)acetate

Product 1

HCID 862816285-(3,5-Dimethylisoxazol-4-yl)-3-(4-(2-hydroxyethyl)piperazin-1-yl)-3-phenylindolin-2-oneYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Ethyl 2-(4-(5-(3,5-dimethylisoxazol-4-yl)-2-oxo-3-phenylindolin-3-yl)piperazin-1-yl)acetate (100 mg, 0.21 mmol) in THF (5 mL) was added lithium aluminium tetrahydride (38 mg, 1.05 mmol) at 0° C., the reaction mixture was stirred at RT for 2.0 h. After cooling to 0° C., the reaction was quenched by addition of aq. saturated NH4Cl solution (50 mL). The mixture was diluted with water and extracted with EtOAc (50 mL). The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and evaporated in vacuo to yield crude product which were purified on flash column chromatography to afford the title compound as a white solid (30 mg, 33%). 1H NMR (400 MHz, DMSO-d6): δ H 10.69 (s, 1H), 7.22-7.51 (m, 7H), 6.96 (d, J=8.0 Hz, 1H), 4.31 (s, 1H), 3.40-3.45 (m, 2H), 2.13-2.40 (m, 13H), 2.02 (s, 3H). MS (ESI) m/e [M+1]+ 433.

Workup

  1. temperatureAfter cooling to 0° C.
  2. customthe reaction was quenched by addition of aq. saturated NH4Cl solution (50 mL)
  3. additionThe mixture was diluted with water
  4. extractionextracted with EtOAc (50 mL)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto yield crude product which
  10. customwere purified on flash column chromatography

Sources & evidence

ORD record
ord-900ab26453424e29bbbab3e4393a6dad
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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