Piperidine → 3-((3-((E)-2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)methylene)indolin-2-one

HRID 1615351Notes

Reaction equation

HRID 1615351 reaction equation
N1CCCCC1.[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][C:8]1=[O:16].[N:17]1[CH:22]=[CH:21][C:20](/[CH:23]=[CH:24]/[C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([CH:34]=O)[CH:32]=3)[N:27]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:26]=2)=[CH:19][CH:18]=1>CCO>[N:17]1[CH:22]=[CH:21][C:20](/[CH:23]=[CH:24]/[C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([CH:34]=[C:9]4[C:10]5[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=5)[NH:7][C:8]4=[O:16])[CH:32]=3)[N:27]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:26]=2)=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 321710OxindoleHCID 86651988(E)-3-(2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carbaldehyde

Product 1

HCID 698107823-((3-((E)-2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)methylene)indolin-2-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

A solution of piperidine (0.2M in EtOH, 0.10 mL, 0.02 mmol) was added to a suspension of oxindole (16.5 mg, 0.12 mmol) and (E)-3-(2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carbaldehyde (42.5 mg, 0.11 mmol) in EtOH (4 mL). The reaction was then heated to 75° C. for 15 hrs. The solvent was evaporated in vacuo. MeOH was added and the resulting suspension was sonicated, but the solution was still cloudy even after EtOAc was added. The solid was removed by filtration and the solvent evaporated in vacuo. Chromatography (5 g silica SPE tube, Silicycle, 2% MeOH in CH2Cl2) gave a yellow solid (35 mg, 64%, 55:45 mixture of E/Z isomers). 1H NMR (400 MHz, CDCl3 plus a drop of CD3OD) δ 9.77 (s, 0.45H), 8.63 (m, 1.9H), 8.42 (s, 0.55H), 8.18 (s, 0.45H), 8.14 (dd, J=8.8, 1.2 Hz, 0.45H), 8.00 (s, 1H), 7.83-7.42 (m, 7H), 7.26 (t, J=7.6 Hz, 1H), 7.09 (t, J=7.6 Hz, 0.45H), 6.94-6.88 (m, 1.6H), 5.80 (s, 0.55H), 5.77 (s, 0.45H), 3.64 (m, 2H), 0.95 (m, 2H), −0.02 (s, 5H), −0.03 (s, 4H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. additionMeOH was added
  3. customthe resulting suspension was sonicated
  4. additionwas added
  5. customThe solid was removed by filtration
  6. customthe solvent evaporated in vacuo
  7. customChromatography (5 g silica SPE tube, Silicycle, 2% MeOH in CH2Cl2) gave
  8. additiona yellow solid (35 mg, 64%, 55:45 mixture of E/Z isomers)

Sources & evidence

ORD record
ord-053691b8c80e482ea571d3864b305e5f
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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