Dimethylamine → 5-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-3-(2-oxocyclohexyl)indolin-2-one

HRID 1052956Notes

Reaction equation

HRID 1052956 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=[O:17])=[C:5]([CH3:18])[O:4][N:3]=1.[C:19]1(=[O:25])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.CNC>CO>[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([OH:17])[CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][C:19]2=[O:25])=[C:5]([CH3:18])[O:4][N:3]=1

Participants

5

Reactant 3

HCID 674DimethylamineHCID 7967CyclohexanoneHCID 1175999855-(3,5-Dimethylisoxazol-4-yl)indoline-2,3-dione

Product 1

HCID 1176680705-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-3-(2-oxocyclohexyl)indolin-2-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

5-(3,5-dimethylisoxazol-4-yl)indoline-2,3-dione (242 mg, 1.0 mmol) is dissolved in MeOH (20 ml), cyclohexanone (196 mg, 2.0 mmol) and dimethylamine (0.4 mmol) are added and the reaction mixture is stirred for 4 h at room temperature. After that, the mixture is concentrated in vacuo and the residue was purified with chromatography on column to give two isomers (The first 50 mg, 14.7%, the second 30 mg, 8.8% and mixture 100 mg, 29.3%). The fast isomer (50 mg, 14.7%): 1H NMR (400 MHz, DMSO-d6): δ 10.25 (s, 1H), 7.29 (d, J=1.6 Hz, 1H), 7.17 (dd, J=1.6, 8.0 Hz, 1H), 6.84 (d, J=8.0 Hz, 1H), 5.83 (s, 1H), 3.32-3.41 (m, 1H), 2.30-2.40 (m, 5H), 2.19 (s, 3H), 1.98-2.06 (m, 2H), 1.80-1.83 (m, 2H), 1.44-1.64 (m, 2H), MS (ESI) m/e [M+1]+ 341.0; the slow isomer (30 mg, 8.8%): 1H NMR (400 MHz, DMSO-d6): δ 10.31 (s, 1H), 7.16-7.20 (m, 2H), 6.88 (d, J=8.0 Hz, 1H), 5.92 (s, 1H), 3.08-3.12 (m, 1H), 2.59-2.62 (m, 1H), 2.36 (s, 3H), 2.29-2.35 (m, 1H), 2.19 (s, 3H), 1.77-2.00 (m, 4H), 1.62-1.68 (m, 1H), 1.42-1.50 (m, 1H), MS (ESI) m/e [M+1]+ 341.

Workup

  1. concentrationAfter that, the mixture is concentrated in vacuo
  2. customthe residue was purified with chromatography on column
  3. customto give two isomers (The first 50 mg, 14.7%

Sources & evidence

ORD record
ord-87fef7331da4412caef784a9bccee8c5
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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